bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations of Plasma Angiopoietins-1 and -2 and Angiopoietin-2/-1 Ratios With Measures of Organ Injury and Clinical Outcomes in Children With Sepsis: A Preliminary Report
Authors: Richter Robert P. , Zheng Lei , Ashtekar Amit R. , Walker Shannon C. , Pittet Jean-Francois , Richter Jillian R. 
Published: July 2020

Objectives:
Results from preclinical and adult sepsis studies suggest that the balance of circulating angiopoietin-1 and -2 levels, represented as angiopoietin-2/-1 ratios, plays a pivotal role in mediating vascular dysfunction and organ injury during sepsis. However, the relationship of plasma angiopoietins with organ injury and clinical outcomes in children with sepsis remains unknown. We sought to determine whether plasma angiopoietin-1 and -2 levels and angiopoietin-2/-1 ratios in the acute phase of sepsis correlated with measures of organ injury and clinical outcomes in children with sepsis.

Design:
Prospective observational cohort study.

Setting:
PICU within a tertiary freestanding children’s hospital.

Patients:
Children 18 years old or less and greater than 3 kg admitted to the PICU for sepsis.

Interventions:
None.

Measurements and Main Results:
Plasma angiopoietin-1 and -2 levels were measured in 38 children with sepsis 0–6, 24, 48, and 72 hours following PICU admission. Children with elevated pediatric Sequential Organ Failure Assessment scores on the third day after PICU admission demonstrated significantly higher 24–72-hour angiopoietin-2/-1 ratios predominantly as a function of higher angiopoietin-2 levels. In children with sepsis-induced organ dysfunction, angiopoietin-2/-1 ratios correlated with oxygenation indices and serum levels of creatinine and bilirubin. Forty-eight- and 72-hour angiopoietin-2/-1 ratios correlated with PICU length of stay (Spearman rho = 0.485, p = 0.004 and rho = 0.440, p = 0.015, respectively).

Conclusions:
In the acute phase of sepsis in children, plasma angiopoietin-2/-1 ratios rise significantly above control levels and correlate with measures of organ injury and worse clinical outcomes after 24 hours. Our findings suggest that angiopoietin dysregulation begins early in sepsis and, if sustained, may promote greater organ injury that can lead to worse clinical outcomes.
Ferrimonas sediminicola sp. nov. and Ferrimonas aestuarii sp. nov., Fe(III)-reducing bacteria isolated from marine environments
Authors: Hwang Juchan , Song Jaeho , Lim Yeonjung , Joung Yochan , Cho Jang-Cheon 
Published: July 2020

Two Gram-stain-negative, Fe(III)-reducing, facultatively anaerobic, motile via a single polar flagellum, rod-shaped bacterial strains, designated IMCC35001T and IMCC35002T, were isolated from tidal flat sediment and seawater, respectively. Results of 16S rRNA gene sequence analysis showed that IMCC35001T and IMCC35002T shared 96.6 % sequence similarity and were most closely related to

Ferrimonas futtsuensis

FUT3661T (98.6 %) and

Ferrimonas kyonanensis

Asr22-7T (96.8 %), respectively. Draft genome sequences of IMCC35001T and IMCC35002T revealed 4.0 and 4.8 Mbp of genome size with 61.0 and 51.8 mol% of DNA G+C content, respectively. Average nucleotide identity (ANI) and digital DNA–DNA hybridization (dDDH) values between the two strains were 73.1 and 19.8 %, respectively, indicating that they are separate species. The two genomes showed ≤84.4 % ANI and ≤27.8 % dDDH to other species of the genus

Ferrimonas

, suggesting that the two strains each represent novel species. The two strains contained both menaquinone (MK-7) and ubiquinones (Q-7 and Q-8). Major fatty acids of strain IMCC35001T were iso-C15 : 0, C18 : 1
ω9c, C17 : 1
ω8c and C16 : 0 and those of strain IMCC35002 T were C18 : 1
ω9c, C16 : 0 and summed feature 3 (C16 : 1
ω7c and/or C16 : 1
ω6c). Major polar lipids in both strains were phosphatidylethanolamine, phosphatidylglycerol, unidentified phospholipid, unidentified aminophospholipid and unidentified lipids. The two strains reduced Fe(III) citrate, Fe(III) oxyhydroxide, Mn(IV) oxide and sodium selenate but did not reduce sodium sulfate. They were also differentiated by several phenotypic characteristics. Based on the polyphasic taxonomic data, IMCC35001T and IMCC35002T were considered to represent each novel species in the genus

Ferrimonas

, for which the names Ferrimonas sediminicola sp. nov. (IMCC35001T=KACC 21161T=NBRC 113699T) and Ferrimonas aestuarii (IMCC35002T=KACC 21162T=NBRC 113700T) sp. nov. are proposed.
Use of a humanized anti-CD6 monoclonal antibody (itolizumab) in elderly patients with moderate COVID-19
Authors: Díaz Yayquier , Ramos-Suzarte Mayra , Martín Yordanis , Calderón Néstor Antonio , Santiago William , Viñet Orlando , La O Yulieski , Pérez Jorge , Oyarzábal Augusto , Pérez Yoan , Lorenzo Geidy , Cepeda Meylan , Saavedra Danay , Mazorra Zaima , Estevez Daymys , Lorenzo-Luaces Patricia , Valenzuela Carmen , Caballero Armando , Leon Kalet , Crombet Tania , Hidalgo Carlos Jorge 
Published: July 2020

AbstractIntroductionThe Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused a recent outbreak of Coronavirus Disease (COVID-19). In Cuba, the first case of COVID-19 was reported on March 11. Elderly with multiple comorbidities are particularly susceptible to adverse clinical outcomes in the course of SARS CoV-2 infection. During the outbreak, a local transmission event took place in a nursing home in Villa Clara province, Cuba, in which nineteen elderly residents were positive for SARS-CoV-2.MethodsBased on the increased susceptibility to viral-induced cytokine release syndrome inducing respiratory and systemic complications in this population, the patients were included in an expanded access clinical trial to receive itolizumab, an anti-CD6 monoclonal antibody.ResultsAll the patients had underlying medical conditions. The product was well tolerated. After the first dose, the course of the disease was favorable and 18 out of 19 (94.7%) patients were discharged clinically recovered with negative RT-PCR at 13 days (median). One dose of itolizumab, circulating IL-6 decreased in the first 24-48 hours in patients with high baseline values, whereas in patients with low levels, this concentration remained over low values. To preliminary assess the effect of itolizumab, a control group was selected among the Cuban COVID-19 patients, which did not receive immunomodulatory therapy. Control subjects were well-matched regarding age, comorbidities and severity of the disease. Every three moderately ill patients treated with itolizumab, one admission in intensive care unit (ICU) was prevented.Discussion/ConclusionItolizumab was well tolerated. Its effect is associated with a reduction and controlling IL-6 serum levels. Moreover, treated patients had a favorable clinical outcome, considering their poor prognosis. This treatment is associated significantly with a decrease the risk to be admitted in ICU and reduced 10 times the risk of death. This study corroborates that the timely use of itolizumab, in combination with other antiviral and anticoagulant therapies, is associated with a reduction the COVID-19 disease worsening and mortality. The humanized antibody itolizumab emerges as a therapeutic alternative for patients with COVID-19 and suggests its possible use in patients with cytokine release syndrome from other pathologies.
High-resolution temporal transcript profiling duringArabidopsis thalianagynoecium morphogenesis uncovers the chronology of gene regulatory network activity and reveals novel developmental regulators
Authors: Kivivirta Kimmo I. , Herbert Denise , Roessner Clemens , de Folter Stefan , Marsch-Martinez Nayelli , Becker Annette 
Published: July 2020

AbstractThe gynoecium is the most complex organ formed by the flowering plants. It encloses the ovules, provides a surface for pollen contact and self-incompatibility reactions, allows pollen tube growth and, post fertilization, and develops into the fruit. Consequently, the regulation of gynoecium morphogenesis is complex and appropriate timing of this process in part determines reproductive success. However, little is known about the global control of gynoecium development, even though many regulatory genes have been characterized. Here, we characterized dynamic gene expression changes using laser-microdissected gynoecium tissue from four developmental stages in Arabidopsis. We provide a high-resolution map of global expression dynamics during gynoecium morphogenesis and link these to the gynoecium interactome. We reveal groups of genes acting together early and others acting late in morphogenesis. Clustering of co-expressed genes enables comparisons between the leaf, shoot apex, and gynoecium transcriptomes allowing the dissection of common and distinct regulators. Furthermore, our results lead to the discovery of theLESSER FERTILITY1-4(LEF1-4) genes, which, when mutated, lead to impaired gynoecium expansion, illustrating that global transcriptome analyses reveal yet unknown developmental regulators. Our data show that highly interacting proteins, such asSEPALLATA3, AGAMOUS, andTOPLESSare expressed more evenly during development, but switch interactors in time, whereas stage-specific proteins have only few interactors. Our analysis connects specific transcriptional regulator activities, protein interactions, and underlying metabolic processes towards the development of a dynamic network model for gynoecium development.
Genetic Code Evolution Reconstructed with Aligned Metrics
Authors: Davis Brian K. 
Published: July 2020

AbstractSequence homology in pre-divergence tRNA species revealed cofactor/adaptors cognate for 16 amino acids derived from oxaloacetate, pyruvate, phosphoglycerate, or phosphoenolpyruvate were related. Synthesis path-distances of these amino acids correlated with phylogenetic depth, reflecting relative residue frequency in pre-divergence sequences. Both metrics were thus aligned in the four sub-families of the Aspartate family, and misaligned in the small Glutamate family; a functional difference was noted and seen to parallel synthetase duality. Amino acid synthetic order, based on path-distances, indicate NH4+fixer amino acids, Asp1, Asn2, and homologues, Glu1, Gln2, formed the first code. Together with a termination signal, they acquired all four triplet 4-sets in the XAN column (X, 5’ coding site; N, any 3’-base). An invariant mid-A conformed with pre-code translation on a poly(A) template by a ratchet-equipped ribosome resulting in random, polyanionic polypeptides. Code expansion occurred in a compact (mutation minimizing) columnwise pattern, (XAN) ➔ XCN ➔ XGN ➔ XUN; with increasing mean path-distance, (1.5) ➔ 4 ➔ 5 ➔ 7 steps; amino acid side-chain hydrophobicity, (+6.6) ➔ −0.8 ➔ −1.5 ➔ −3.2 kcal/ mol; codon:anticodon H bond enthalpy (selection for bond-strength), (−12.5) ➔ −17.5 ➔ −15.5 ➔ −14.5 kcal/ mol; and precursorspecific 5’-base, A, oxaloacetate, G, pyruvate/oxaloacetate, U, phosphoglycerate/oxaloacetate, C, oxoglutarate, forming horizontal code domains. Codon bias evidence corroborated the XCN ➔ XGN step in expansion, and revealed row GNN coevolved with ANN, on correction for overprinting. Extended surfaceattachment (Fajan-Paneth principle) by pro-Fd[5] and bilayer partitioning by H+ATPase proteolipid-h1 subunit implicated expansion phase proteins in driving increases in side-chain hydrophobicity during code expansion. 3’-Base recruitment in pre-assigned codon boxes added six long (9-to 14-step) path amino acid, bearing a basic, or cyclic, side-chain; 3 of 4 polar, post-expansion amino acids acquired polar cluster NAN codons and 2 of 3 non-polar (Ile7included) acquired non-polar cluster NUN codons, yieldng a split-box pair homology ofp= 5.4×10-3. All eight overprinted codon boxes (GAYRfor Asp1, Glu1included) exhibit weak codon:anticodon H-bond enthalpy, −14 kcal/mol or higher, in three of six distinct code enthalpy states.
Protein Interaction Patterns inArabidopsis thalianaLeaf Mitochondria Change in Response to Illumination
Authors: Rugen Nils , Schaarschmidt Frank , Braun Hans-Peter , Eubel Holger 
Published: July 2020

AbstractMitochondrial biology is underpinned by the presence and activity of large protein complexes participating in the organelle-located parts of cellular respiration, the TCA cycle and oxidative phosphorylation. While the enzymatic roles of these complexes are undisputed, little is known about the interactions of the subunits beyond their presence in the monomeric protein complexes and their functions in regulating mitochondria metabolism. By applying one of the most important regulatory cues for plant metabolism, the presence or absence of light, we here assess the changes in the composition and molecular mass of known mitochondrial protein complexes by employing a differential complexome profiling strategy. Covering a mass range up to 25 MDa, we demonstrate dynamic associations of TCA-cycle enzymes and of OXPHOS components. The data presented here form the basis for future studies aiming to advance our understanding of the role of protein:protein interactions in the regulation of plant mitochondrial functions.
Inference of long-range cell-cell force transmission from ECM remodeling fluctuations
Authors: Nahum Assaf , Koren Yoni , Ergaz Bar , Natan Sari , Miller Gad , Tamir Yuval , Goren Shahar , Kolel Avraham , Jagadeeshan Sankar , Elkabets Moshe , Lesman Ayelet , Zaritsky Assaf 
Published: July 2020

AbstractCells sense, manipulate and respond to their mechanical microenvironment in a plethora of physiological processes, yet the understanding of how cells transmit, receive and interpret environmental cues to communicate with distant cells is severely limited due to lack of tools to quantitatively infer the complex tangle of dynamic cell-cell interactions in complicated environments. We present a computational method to systematically infer and quantify long-range cell-cell force transmission through the extracellular matrix (cell-ECM-cell communication) by correlating ECM remodeling fluctuations in between communicating cells and demonstrating that these fluctuations contain sufficient information to define unique signatures that robustly distinguish between different pairs of communicating cells. We demonstrate our method with finite element simulations and live 3D imaging of fibroblasts and cancer cells embedded in fibrin gels. While previous studies relied on the formation of a visible fibrous ‘band’ extending between cells to inform on mechanical communication, our method detected mechanical propagation even in cases where visible bands never formed. We revealed that while contractility is required, band formation is not necessary, for cell-ECM-cell communication, and that mechanical signals propagate from one cell to another even upon massive reduction in their contractility. Our method sets the stage to measure the fundamental aspects of intercellular long-range mechanical communication in physiological contexts and may provide a new functional readout for high content 3D image-based screening. The ability to infer cell-ECM-cell communication using standard confocal microscopy holds the promise for wide use and democratizing the method.
A Multi-Phenotype System to Discover Therapies for Age-Related Dysregulation of the Immune Response to Viral Infections
Authors: White Brandon , Komalo Ben , Nicolaisen Lauren , Donne Matt , Marsh Charlie , DeVay Rachel M. , Nguyen An M. , Cousin Wendy , Heinrich Jarred , Van Trump William J. , Plott Tempest , Fuller Colin J. , Nguyen Dat , Chen Daniel , Bucher Delia , Tyrra Sabine , Haynes Laura , Kuchel George , Goronzy Jorg , Larbi Anis , Fulop Tamas , Heiser Diane , Schwandner Ralf , Elabd Christian , Kamens Ben 
Published: July 2020

ABSTRACTAge-related immune dysregulation contributes to increased susceptibility to infection and disease in older adults. We combined high-throughput laboratory automation with machine learning to build a multi-phenotype aging profile that models the dysfunctional immune response to viral infection in older adults. From a single well, our multi-phenotype aging profile can capture changes in cell composition, physical cell-to-cell interaction, organelle structure, cytokines, and other hidden complexities contributing to age-related dysfunction. This system allows for rapid identification of new potential compounds to rejuvenate older adults’ immune response. We used our technology to screen thousands of compounds for their ability to make old immune cells respond to viral infection like young immune cells. We observed beneficial effects of multiple compounds, of which two of the most promising were disulfiram and triptonide. Our findings indicate that disulfiram could be considered as a treatment for severe coronavirus disease 2019 and other inflammatory infections.
Organ geometry channels cell fate in the Arabidopsis ovule primordium
Authors: Hernandez-Lagana Elvira , Mosca Gabriella , Sato Ethel Mendocilla , Pires Nuno , Frey Anja , Giraldo-Fonseca Alejandro , Grossniklaus Ueli , Hamant Olivier , Godin Christophe , Boudaoud Arezki , Grimanelli Daniel , Autran Daphné , Baroux Célia 
Published: July 2020

SummaryIn multicellular organisms, sexual reproduction requires the separation of the germline from the soma. In flowering plants, the first cells of the germline, so-called spore mother cells (SMCs), differentiate as the reproductive organs form. Here, we explored how organ growth influences and contributes to SMC differentiation. We generated a collection of 92 annotated 3D images capturing ovule primordium ontogeny at cellular resolution in Arabidopsis. We identified a spatio-temporal pattern of cell divisions that acts in a domain-specific manner as the primordium forms, which is coupled with the emergence of a single SMC. Using tissue growth models, we uncovered plausible morphogenetic principles involving a spatially confined growth signal, differential mechanical properties, and cell growth anisotropy. Our analysis also reveals that SMC characteristics first arise in more than one cell but SMC fate becomes progressively restricted to a single cell during organ growth. Altered primordium geometry coincided with a delay in this fate restriction process inkataninmutants. Altogether, our study suggests that tissue geometry canalizes and modulates reproductive cell fate in the Arabidopsis ovule primordium.
The input-output relation of primary nociceptive neurons is determined by the morphology of the peripheral nociceptive terminals
Authors: Barkai Omer , Butterman Rachely , Katz Ben , Lev Shaya , Binshtok Alexander M. 
Published: July 2020

AbstractThe output from the peripheral terminals of primary nociceptive neurons, which detect and encode the information regarding noxious stimuli, is crucial in determining pain sensation. The nociceptive terminal endings are morphologically complex structures assembled from multiple branches of different geometry, which converge in a variety of forms to create the terminal tree. The output of a single terminal is defined by the properties of the transducer channels producing the generation potentials and voltage-gated channels, translating the generation potentials into action potential firing. However, in the majority of cases, noxious stimuli activate multiple terminals; thus, the output of the nociceptive neuron is defined by the integration and computation of the inputs of the individual terminals. Here we used a computational model of nociceptive terminal tree to study how the architecture of the terminal tree affects input-output relation of the primary nociceptive neurons. We show that the input-output properties of the nociceptive neurons depend on the length, the axial resistance, and location of individual terminals. Moreover, we show that activation of multiple terminals by capsaicin-like current allows summation of the responses from individual terminals, thus leading to increased nociceptive output. Stimulation of terminals in simulated models of inflammatory or nociceptive hyperexcitability led to a change in the temporal pattern of action potential firing, emphasizing the role of temporal code in conveying key information about changes in nociceptive output in pathological conditions, leading to pain hypersensitivity.Significance statementNoxious stimuli are detected by terminal endings of the primary nociceptive neurons, which are organized into morphologically complex terminal trees. The information from multiple terminals is integrated along the terminal tree, computing the neuronal output, which propagates towards the CNS, thus shaping the pain sensation. Here we revealed that the structure of the nociceptive terminal tree determines the output of the nociceptive neurons. We show that the integration of noxious information depends on the morphology of the terminal trees and how this integration and, consequently, the neuronal output change under pathological conditions. Our findings help to predict how nociceptive neurons encode noxious stimuli and how this encoding changes in pathological conditions, leading to pain.
Mapping the landscape of chromatin dynamics during naïve CD4+ T-cell activation
Authors: Iqbal Muhammad Munir , Serralha Michael , Kaur Parwinder , Martino David 
Published: July 2020

AbstractT-cell activation induces context-specific gene expression programs that promote energy generation and biosynthesis, progression through the cell cycle and ultimately cell differentiation. The aim of this study was to apply the omni ATAC-seq method to characterize the landscape of chromatin changes induced by T-cell activation in mature naïve CD4+ T-cells. Using a well-established ex vivo protocol of canonical T-cell receptor signaling, we generated genome-wide chromatin maps of naïve T-cells from pediatric donors in quiescent or recently activated states. We identified thousands of individual chromatin accessibility peaks that are associated with T-cell activation. The majority of these were localized to intronic and intergenic enhancer regions, marked by active histone modifications whilst quiescence was maintained by repressive histone marks. Regions of activation-associated gains in chromatin accessibility were enriched for well-known pioneer transcription factor motifs, and super-enhancer regions associated with distinct gene regulatory networks. Thesecis-regulatory elements together brought about distinct transcriptional signatures in activated cells including TNFa-NFkB signaling, hormone-responsive genes, inflammatory response genes and IL2-STAT5 signaling. Our data provides novel insights into the chromatin dynamics and motif usage of T-cell receptor signaling events in early life. The characterized pathways demonstrate the utility of chromatin profiling techniques applied to bio-banked samples for characterizing gene regulatory elements.