bluuebunny/crossref_metadata_2025 huggingface dataset:
Consensus Statement on the Management of Waldenström Macroglobulinemia Patients During the COVID‐19 Pandemic
Authors: Talaulikar Dipti , Advani Ranjana H. , Branagan Andrew R. , Buske Christian , Dimopoulos Meletios A. , D'Sa Shirley , Kersten Maria J. , Leblond Veronique , Minnema Monique C. , Owen Roger G. , Palomba Maria Lia , Tedeschi Alessandra , Trotman Judith , Varettoni Marzia , Vos Josephine M. , Treon Steven P. , Kastritis Efstathios , Castillo Jorge J.
Published: July 2020

In the light of the COVID‐19 pandemic, the International Workshop on Waldenström Macroglobulinemia (IWWM) Treatment Recommendations Panel felt the need to provide a consensus statement for the management of Waldenström Macroglobulinemia (WM) patients during this challenging time. We followed the current recommendations by the American Society of Hematology, which have been modified accordingly to fit the specific realities associated with the management of WM. In this Consensus Statement, the Panel addresses questions related to treatment initiation, preferred therapies, minimizing visit to clinics and infusions centers, supportive care and guidance for WM patients in clinical trials. Finally, we also provide information on timing and appropriateness of testing and management of COVID‐19 infected patients, as well as ways to get physicians and patients involved in registry studies that could help others.
In Vitro Testing and Comparison of Additively Manufactured Polymer Impellers for the CentriMag Blood Pump
Authors: von Petersdorff-Campen Kai , Abeken Jonas , de Zélicourt Diane , Kurtcuoglu Vartan , Meboldt Mirko , Schmid Daners Marianne
Published: July 2020

Additive manufacturing (AM) is an effective tool for accelerating knowledge gain in development processes, as it enables the production of complex prototypes at low cost and with short lead times. In the development of mechanical circulatory support, the use of cheap polymer-based AM techniques for prototype manufacturing allows more design variations to be tested, promoting a better understanding of the respective system and its optimization parameters. Here, we compare four commonly used AM processes for polymers with respect to manufacturing accuracy, surface roughness, and shape fidelity in an aqueous environment. Impeller replicas of the CentriMag blood pump were manufactured with each process and integrated into original pump housings. The assemblies were tested for hydraulic properties and hemolysis in reference to the commercially available pump. Computational fluid dynamic simulations were carried out to support the transfer of the results to other applications. In hydraulic testing, the deviation in pressure head and motor current of all additively manufactured replicas from the reference pump remained below 2% over the entire operating range of the pump. In contrast, significant deviations of up to 620% were observed in hemolysis testing. Only the replicas produced by stereolithography showed a nonsignificant deviation from the reference pump, which we attribute to the low surface roughness of parts manufactured thereby. The results suggest that there is a flow-dependent threshold of roughness above which a surface strongly contributes to cell lysis by promoting a hydraulically rough boundary flow.
Dietary Supplement Use in the United States
Authors: Moore Jeff , McClain Amanda , Hong Mee Young
Published: July 2020

The history and trends in use of dietary supplements as documented in the National Health and Nutrition Examination Survey are summarized. The safety and efficacy of selected supplements are discussed. The current regulation of dietary supplements is not robust because legislation governing enforcement is weaker than it is for drugs.
Risk Communication in the Time of COVID
Authors: Rowe Sylvia , Alexander Nick
Published: July 2020

With the nightmare memory of the 2019–2020 coronavirus plague still fresh in health communicators' minds, it may be time for some thoughtful reflection. Are there any useful lessons nutrition and food science communicators can take away from the early experiences of the public health community in talking about risk? In the present article, the authors review the long-confirmed rules of risk communication under crisis conditions; they analyze the practices followed and messages delivered in the early stages of the coronavirus pandemic, and they analyze the almost astonishing effect of these communications on the public's behavioral attitudes. Offered as well are some possible lessons for nutrition communicators going forward: for example, food communicators might gain increased understanding of the need for empathy in talking to their audiences and of the importance of crafting messages that cut through the clutter of limited or inaccurate information. They propose some enhanced guidelines to improve crisis communication lines—experts to consumers to experts—going forward.
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.
Comparative genome analysis of Erysipelothrix rhusiopathiae isolated from domestic pigs and wild boars suggests host adaptation and selective pressure from the use of antibiotics
Authors: Söderlund Robert , Formenti Nicoletta , Caló Stefania , Chiari Mario , Zoric Mate , Alborali Giovanni Loris , Sørensen Dalgaard Tina , Wattrang Eva , Eriksson Helena
Published: July 2020

The disease erysipelas caused by

Erysipelothrix rhusiopathiae

(ER) is a major concern in pig production. In the present study the genomes of ER from pigs (n=87), wild boars (n=71) and other sources (n=85) were compared in terms of whole-genome SNP variation, accessory genome content and the presence of genetic antibiotic resistance determinants. The aim was to investigate if genetic features among ER were associated with isolate origin in order to better estimate the risk of transmission of porcine-adapted strains from wild boars to free-range pigs and to increase our understanding of the evolution of ER. Pigs and wild boars carried isolates representing all ER clades, but clade one only occurred in healthy wild boars and healthy pigs. Several accessory genes or gene variants were found to be significantly associated with the pig and wild boar hosts, with genes predicted to encode cell wall-associated or extracellular proteins overrepresented. Gene variants associated with serovar determination and capsule production in serovars known to be pathogenic for pigs were found to be significantly associated with pigs as hosts. In total, 30 % of investigated pig isolates but only 6 % of wild boar isolates carried resistance genes, most commonly tetM (tetracycline) and lsa(E) together with lnu(B) (lincosamides, pleuromutilin and streptogramin A). The incidence of variably present genes including resistance determinants was weakly linked to phylogeny, indicating that host adaptation in ER has evolved multiple times in diverse lineages mediated by recombination and the acquisition of mobile genetic elements. The presented results support the occurrence of host-adapted ER strains, but they do not indicate frequent transmission between wild boars and domestic pigs. This article contains data hosted by Microreact.
Defining the transcriptional responses of Aspergillus nidulans to cation/alkaline pH stress and the role of the transcription factor SltA
Authors: Picazo Irene , Etxebeste Oier , Requena Elena , Garzia Aitor , Espeso Eduardo Antonio
Published: July 2020

Fungi have developed the ability to overcome extreme growth conditions and thrive in hostile environments. The model fungus Aspergillus nidulans tolerates, for example, ambient alkalinity up to pH 10 or molar concentrations of multiple cations. The ability to grow under alkaline pH or saline stress depends on the effective function of at least three regulatory pathways mediated by the zinc-finger transcription factor PacC, which mediates the ambient pH regulatory pathway, the calcineurin-dependent CrzA and the cation homeostasis responsive factor SltA. Using RNA sequencing, we determined the effect of external pH alkalinization or sodium stress on gene expression. The data show that each condition triggers transcriptional responses with a low degree of overlap. By sequencing the transcriptomes of the null mutant, the role of SltA in the above-mentioned homeostasis mechanisms was also studied. The results show that the transcriptional role of SltA is wider than initially expected and implies, for example, the positive control of the PacC-dependent ambient pH regulatory pathway. Overall, our data strongly suggest that the stress response pathways in fungi include some common but mostly exclusive constituents, and that there is a hierarchical relationship among the main regulators of stress response, with SltA controlling pacC expression, at least in A. nidulans.
Activation of a [NiFe]-hydrogenase-4 isoenzyme by maturation proteases
Authors: Finney Alexander J. , Buchanan Grant , Palmer Tracy , Coulthurst Sarah J. , Sargent Frank
Published: July 2020

Maturation of [NiFe]-hydrogenases often involves specific proteases responsible for cleavage of the catalytic subunits.

Escherichia coli

HycI is the protease dedicated to maturation of the Hydrogenase-3 isoenzyme, a component of formate hydrogenlyase-1. In this work, it is demonstrated that a

Pectobacterium atrosepticum

HycI homologue, HyfK, is required for hydrogenase-4 activity, a component of formate hydrogenlyase-2, in that bacterium. The

P. atrosepticum

ΔhyfK mutant phenotype could be rescued by either P. atrosepticum hyfK or E. coli hycI on a plasmid. Conversely, an

E. coli

ΔhycI mutant was complemented by either E. coli hycI or P. atrosepticum hyfK in trans. E. coli is a rare example of a bacterium containing both hydrogenase-3 and hydrogenase-4, however the operon encoding hydrogenase-4 has no maturation protease gene. This work suggests HycI should be sufficient for maturation of both

E. coli

formate hydrogenlyases, however no formate hydrogenlyase-2 activity was detected in any

E. coli

strains tested here.
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

Introduction

The 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.

Methods

Based 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.

Results

All 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/Conclusion

Itolizumab 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

The 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

Sequence 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

Mitochondrial 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

Cells 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

Age-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

In 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

The 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 statement

Noxious 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

T-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.
The role of habitat configuration in shaping animal population processes: a framework to generate quantitative predictions
Authors: He Peng , Montiglio Pierre-Olivier , Somveille Marius , Cantor Mauricio , Farine Damien R.
Published: July 2020

By shaping where individuals move, habitat configuration can fundamentally structure animal populations. Yet, we currently lack a framework for generating quantitative predictions about the role of habitat configuration in modulating population outcomes. For example, it is well known that the social structure of animal populations can shape spreading dynamics, but it remains underexplored to what extent such dynamics are determined by the underlying habitat configuration. To address this gap, we propose a framework and model inspired by studies using networks to characterize habitat connectivity. We first define animal habitat networks, explain how they can integrate information about the different configurational features of animals’ habitats, and highlight the need for a bottom-up generative model that can depict realistic variations in habitat structural connectivity. Second, we describe a model for simulating animal habitat networks (available in the R packageAnimalHabitatNetwork), and demonstrate its ability to generate alternative habitat configurations based on empirical data, which forms the basis for exploring the consequences of alternative habitat structures. Finally, we use our framework to demonstrate how transmission properties, such as the spread of a pathogen, can be impacted by both local connectivity and landscape-level characteristics of the habitat. Our study highlights the importance of considering the underlying habitat configuration in studies linking social structure with population-level outcomes.
Statistical image processing quantifies the changes in cytoplasmic texture associated with aging inCaenorhabditis elegansoocytes
Authors: Imakubo Momoko , Takayama Jun , Okada Hatsumi , Onami Shuichi
Published: July 2020

Background

Oocyte quality decreases with aging, thereby increasing errors in fertilization, chromosome segregation, and embryonic cleavage. Oocyte appearance also changes with aging, suggesting a functional relationship between oocyte quality and appearance. However, no methods are available to objectively quantify age-associated changes in oocyte appearance.

Results

We show that statistical image processing of Nomarski differential interference contrast microscopy images can be used to quantify age-associated changes inCaenorhabditis elegansoocyte appearance. Max-min Value (mean difference between the maximum and minimum intensities within each moving window) quantitatively characterized the difference in oocyte cytoplasmic texture between 1- and 3-day-old adults (Day 1 and Day 3 oocytes, respectively). With an appropriate parameter set, the gray level co-occurrence matrix (GLCM)-based texture featureCorrelation(COR) more sensitively characterized this difference than the Max-min Value. Manipulating the smoothness of and/or adding irregular structures to the cytoplasmic texture of Day 1 oocyte images reproduced the difference in Max-min Value but not in COR between Day 1 and Day 3 oocytes. Increasing the size of granules in synthetic images recapitulated the age-associated changes in COR. Manual measurements validated that the cytoplasmic granules in oocytes become larger with aging.

Conclusions

The Max-min Value and COR objectively quantify age-related changes inC. elegansoocyte in Nomarski DIC microscopy images. Our methods provide new opportunities for understanding the mechanism underlying oocyte aging.
Transcriptomic signatures of ageing vary in solitary and social forms of an orchid bee
Authors: Séguret Alice C. , Stolle Eckart , Fleites-Ayil Fernando A. , Quezada-Euán José Javier G. , Hartfelder Klaus , Meusemann Karen , Harrison Mark , Soro Antonella , Paxton Robert J.
Published: July 2020

Eusocial insect queens are remarkable in their ability to maximise both fecundity and longevity, thus escaping the typical trade-off between these two traits. In species exhibiting complex eusocial behaviour, several mechanisms have been proposed to underlie the remoulding of the trade-off, such as reshaping of the juvenile hormone pathway, or caste-specific susceptibility to oxidative stress. However, it remains a challenge to disentangle the molecular mechanisms underlying the remoulding of the trade-off in eusocial insects from caste-specific physiological attributes that have subsequently arisen due to their different life histories. Socially plastic species such as the orchid beeEuglossa viridissimarepresent excellent models to address the role of socialityper sein longevity as they allow direct comparisons of solitary and social individuals within a common genetic background. We present data on gene expression and juvenile hormone levels from young and old bees, from both solitary and social nests. We found 940 genes to be differentially expressed with age in solitary females,versusonly 14 genes in social dominant females, and seven genes in subordinate females. We performed a weighted gene co-expression network analysis to further highlight candidate genes related to ageing in this species. Primary “ageing gene” candidates were related to protein synthesis, gene expression, immunity and venom production. Remarkably, juvenile hormone titres did not vary with age or social status. These results represent an important step in understanding the proximate mechanisms underlying the remodeling of the fecundity/longevity trade-off that accompanies the evolutionary transition from solitary life to eusociality.

Significance statement

The remarkably long lifespan of the queens of eusocial insects despite their high reproductive output suggests that they are not subject to the widespread trade-off between fecundity and longevity that governs solitary animal life histories, yet surprisingly little is known of the molecular mechanisms underpinning their longevity. Using a socially plastic bee in which some individuals of a population are social whilst others are solitary, we identified hundreds of candidate genes and related gene networks that are involved in the remoulding of the fecundity/longevity tradeoff. As well as identifying candidate ageing genes, our data suggest that even in incipient stages of sociality there is a marked reprogramming of ageing; long live the queen.
Exceptional stability of a perilipin on lipid droplets depends on its polar residues, suggesting multimeric assembly
Authors: Giménez-Andrés Manuel , Emeršič Tadej , Antoine-Bally Sandra , Antonny Bruno , Derganc Jure , Čopič Alenka
Published: July 2020

Numerous proteins target lipid droplets (LDs) through amphipathic helices (AHs). It is generally assumed that AHs insert bulky hydrophobic residues in packing defects at the LD surface. However, this model does not explain the targeting of perilipins, the most abundant and specific amphipathic proteins of LDs. The gigantic Plin4 contains a highly repetitive AH that lacks bulky hydrophobic residues, and its LD targeting depends strongly on its length. We show that Plin4 forms a remarkably immobile protein layer at the surface of cellular or artificial LDs, making them stable over days. This Plin4 AH feature is not shared with the AHs of other perilipins, which display much faster dynamics on lipid surfaces. Plin4 AH stability on LDs is exquisitely sensitive to the nature and distribution of its polar residues. These results suggest that Plin4 forms stable arrangements of adjacent AHs via polar interactions.
INTERMEDIUM-Cmediates the shade-induced bud growth arrest in barley
Authors: Wang Hongwen , Seiler Christiane , Sreenivasulu Nese , von Wirén Nicolaus , Kuhlmann Markus
Published: July 2020

Tiller formation is a key agronomic determinant for grain yield in cereal crops. The modulation of this trait is controlled by transcriptional regulators and plant hormones, tightly regulated by external environmental conditions. While endogenous (genetics) and exogenous (environmental factors) triggers for tiller formation have mostly been investigated separately, it has remained elusive how they are integrated into the developmental program of this trait. The transcription factorINTERMEDIUM-C (INT-C), which is the barley ortholog of the maize domestication geneTEOSINTE BRANCHED1 (TB1)has a prominent role in regulating tiller bud outgrowth. Here we show thatINT-Cis expressed in tiller buds, required for bud growth arrest in response to shade. In contrast to wild type plants,int-cmutant plants are impaired in their shade response and do not stop tiller production after shading. Gene expression levels ofINT-Care up-regulated under light-limiting growth conditions, and down-regulated after decapitation. Transcriptome analysis of wild-type andint-cbuds under control and shading conditions identified target genes of INT-C that belong to auxin and gibberellin biosynthesis and signaling pathways. Our study identifies INT-C as integrator of the shade response into tiller formation, which is prerequisite for implementing shading responses in the breeding of cereal crops.
Nuclear pores constrict upon energy depletion
Authors: Zimmerli Christian E. , Allegretti Matteo , Rantos Vasileios , Goetz Sara K. , Obarska-Kosinska Agnieszka , Zagoriy Ievgeniia , Halavatyi Aliaksandr , Mahamid Julia , Kosinski Jan , Beck Martin
Published: July 2020

Nuclear pore complexes (NPCs) fuse the inner and outer nuclear membranes and mediate nucleocytoplasmic exchange. They are made of 30 different nucleoporins that form an intricate cylindrical architecture around an aqueous central channel. This architecture is highly dynamic in space and time. Variations in NPC diameter were reported, but the physiological circumstances and the molecular details remain unknown. Here we combined cryo-electron tomography and subtomogram averaging with integrative structural modeling to capture a molecular movie of the respective large-scale conformational changesin cellulo. While actively transporting NPCs adopt a dilated conformation, they strongly constrict upon cellular energy depletion. Fluorescence recovery after photo bleaching experiments show that NPC constriction is concomitant with reduced diffusion and active transport across the nuclear envelope. Our data point to a model where the energy status of cells is linked to the conformation of NPC architecture.
Global RNA sequencing reveals enhanced photosynthetic activity and auxin response inBrassica napustreated withPseudomonas chlororaphisPA23
Authors: Wan Joey C , Becker Michael G , Bolaji Ayooluwa , Walker Philip L , Gray Emma , de Kievit Teresa R , Fernando WG Dilantha , Belmonte Mark F
Published: July 2020

Plant growth promoting bacteria (PGPB) are a growing subset of agricultural adjuncts which can be used to increase crop yield and plant productivity. Although substantial research has been conducted on the metabolites and active molecules secreted by PGPBs, relatively little is known about their effects on the global transcriptome of the host plant. The present study was carried out to investigate changes in the gene expression landscape of early vegetativeBrassica napusfollowing treatment withPseudomonas chlororaphisPA23. This PGPB was isolated from the soybean rhizosphere and has been extensively studied as a biocontrol agent. However, little is known about its effects on plant growth and development. Using a combination of RNA-sequencing and physiological analyses, we identified increased abundance of mRNA transcripts associated with photosynthesis and phytohormone response.

Phenotypically we observed increased photosynthetic rates and larger root and shoot systems inB. napusfollowingP. chlororaphisPA23 treatment. Lastly, we identified auxin production byP. chlororaphisPA23 which likely contributes to changes in gene expression and the observed phenotypic differences in root and shoot structures. Together, the results of our study suggest that PA23 is a potent plant growth promoting agent with the potential for field applications as an agricultural adjunct.
Fragile X Mental Retardation Protein modulates somatic D-type K+channels and action potential threshold in the mouse prefrontal cortex
Authors: Kalmbach Brian E. , Brager Darrin H.
Published: July 2020

Axo-somatic K+channels control action potential output in part by acting in concert with voltage-gated Na+channels to set action potential threshold. Slowly inactivating, D-type K+channels are enriched at the axo-somatic region of cortical pyramidal neurons of the prefrontal cortex where they regulate action potential firing. We previously demonstrated that D-type K+channels are down regulated in extratelencephalic-projecting L5 neurons (ET) in the prefrontal cortex of thefmr1knockout mouse model of Fragile X syndrome (FX mice), resulting in a hyperpolarized action potential threshold. To test whether K+channel alterations are regulated in a cell autonomous manner in FXS, we used a viral-mediated approach to restore expression of Fragile X Mental Retardation Protein (FMRP) in a small population of prefrontal neurons in male FX mice. Outside-out voltage clamp recordings revealed a higher D-type K+conductance in FMRP-positive ET neurons compared to nearby FMRP-negative ET neurons. FMRP did not affect either rapidly inactivating A-type or non-inactivating K+conductance. ET neuron patches recorded with FMRP1-298, a truncated form of FMRP which lacks mRNA binding domains, included in the pipette solution had larger D-type K+conductance compared to heat-inactivated controls. Viral expression of FMRP in FX mice depolarized action potential threshold to near wild type levels in ET neurons. These results suggest that FMRP influences the excitability of ET neurons in the mPFC by regulating somatic D-type K+channels in a cell autonomous, protein-protein dependent manner.