bluuebunny/crossref_metadata_2025 huggingface dataset:
Outflows and extended [C ii] haloes in high-redshift galaxies
Authors: Pizzati E , Ferrara A , Pallottini A , Gallerani S , Vallini L , Decataldo D , Fujimoto S
Published: May 2020

Recent stacked ALMA observations have revealed that normal, star-forming galaxies at z ≈ 6 are surrounded by extended (≈10 kpc) [C ii]-emitting haloes, which are not predicted by the most advanced, zoom-in simulations. We present a model in which these haloes are the result of supernova-driven cooling outflows. Our model contains two free parameters, the outflow mass loading factor, η, and the parent galaxy dark matter halo circular velocity, vc. The outflow model successfully matches the observed [C ii] surface brightness profile if η = 3.20 ± 0.10 and $v_{\rm c} = 170 \pm 10 \, \rm km\, s^{-1}$, corresponding to a dynamical mass of ${\approx }10^{11}\, {\rm M}_{\odot }$. The predicted outflow rate and velocity range are $128 \pm 5\, {\rm M}_{\odot }\, {\rm yr}^{-1}$ and 300–500 $\, \rm km\, s^{-1}$, respectively. We conclude that (a) extended haloes can be produced by cooling outflows; (b) the large η value is marginally consistent with starburst-driven outflows, but it might indicate additional energy input from active galactic nuclei; and (c) the presence of [C ii] haloes requires an ionizing photon escape fraction from galaxies fesc ≪ 1. The model can be readily applied also to individual high-z galaxies, as those observed, e.g. by the ALMA ALPINE survey now becoming available.
A period-dependent spatial scatter of Galactic black hole transients
Authors: Gandhi P , Rao A , Charles P A , Belczynski K , Maccarone T J , Arur K , Corral-Santana J M
Published: May 2020

There remain significant uncertainties in the origin and evolution of black holes in binary systems, in particular regarding their birth sites and the influence of natal kicks. These are long-standing issues, but their debate has been reinvigorated in the era of gravitational wave detections and the improving precision of astrometric measurements. Using recent and archival characterization of Galactic black hole X-ray binaries (BHXBs), we report here an apparent anticorrelation between Porb (system orbital periods) and scatter in $z$ (elevation above the Galactic plane). The absence of long-period sources at high $z$ is not an obvious observational bias, and two possible explanatory scenarios are qualitatively explored: (1) a disc origin for BHXBs followed by natal kicks producing the scatter in $z$, with only the tightest binaries preferentially surviving strong kicks; and (2) a halo origin, with Porb shortening through dynamical interactions in globular clusters (GCs). For the latter case, we show a correspondence in $z$-scatter between BHXBs and the GCs with most compact core radii of <0.1 pc. However, the known absence of outbursting BHXB transients within Galactic GCs remains puzzling in this case, in contrast to the multitude of known GC neutron star XRBs. These results provide an interesting observational constraint for any black hole binary evolutionary model to satisfy.
On game-based control systems and beyond
Authors: Zhang Renren , Wang Fang , Guo Lei
Published: May 2020

This perspective first expounds on the reasons behind the introduction of the game-based control systems (GBCS), delineates their features, provides some examples, and put forward some research problems. The paper then points out that more complex regulation problems on the now rapidly developing man-machine integration systems may also be investigated by expanding the scope of the GBCS.
Ottoman and Egyptian Quarantines and European Debates on Plague in the 1830s–1840s
Authors: Hamed-Troyansky Vladimir
Published: May 2020

In the 1830s, plague, which had been all but forgotten by most Europeans, was on everyone’s lips again. Shortly after the Ottoman and Egyptian governments instituted their first permanent quarantines, the disease broke out in the Levant and the Nile delta, and the global medical community watched anxiously to see whether these new western Mediterranean-style quarantines would be able to contain it within the eastern Mediterranean. By tracing two Russian medical expeditions from the Black Sea port of Odessa to the Ottoman empire and Egypt in the 1840s, this article examines the world of European medical practitioners who engaged in vigorous debates about plague and its prevention. Did the disease have a ‘birthplace’ somewhere in the Middle East? Did it spread through contact with its victims, or was it omnipresent in the bad air? Russian, French, British and other medics questioned old assumptions about plague and its contagiousness, while testing out their hypotheses in Ottoman and Egyptian domains. By the 1840s, the Middle East had become a global site for epidemiological research, driving the internationalization of prevention against epidemic. Meanwhile, Ottoman and Egyptian quarantines, and the elusive nature of plague, became entangled with European political ambitions and commercial interests in the Middle East.
Competition, Markups, and Predictable Returns
Authors: Corhay Alexandre , Kung Howard , Schmid Lukas
Published: May 2020

This paper jointly examines the link between competition and expected returns in the time series and in the cross-section. To this end, we build a general equilibrium model where markups vary because of firm entry with oligopolistic competition. When concentration is high, markups are more sensitive to entry risk. We find that higher markups are associated with higher expected returns over time and across industries, in line with the data. The model can also quantitatively account for the persistent rise in aggregate risk premiums and macroeconomic volatility associated with the secular increase trend industry concentration since the mid-1980s.
Diagnostic value of anti-CD74 antibodies in early and late axial spondyloarthritis and its relationship to disease activity
Authors: Abdelaziz Marwa Mahmoud , Gamal Rania M , Ismail Nadia M , Lafy Raghda A , Hetta Helal F
Published: May 2020

Objectives

This study was designed to evaluate the role of anti-CD74 antibodies in diagnosis of axial spondyloarthritis (axSpA) and their relationship to disease duration and disease activity.

Methods

Fifty patients with axSpA, 15 patients with RA and 15 healthy subjects were included in the study. Clinical examination and laboratory tests were done. The ESR, CRP level and ASDAS were measured as markers of the disease activity. Quantitative determination of human CD74 IgG antibodies was done.

Results

The mean age of the patients was 38.22 (S.D.12.20) years. The level of CD74 autoantibodies was significantly higher in axSpA in comparison to control groups. Most patients with positive articular and extra-articular manifestations were positive for CD74 autoantibodies. In patients with inactive disease, 33.3% were positive for CD74 autoantibodies, as were 83% with active disease. High percentages of patients with early and late axSPA were CD74 autoantibody positive. The majority of patients with positive disease activity in early and late axSpA were CD74 autoantibody positive. CD74 autoantibodies had 80% sensitivity vs both control groups with 87% specificity vs the healthy control group and 80% vs the RA control group in the diagnosis of axSpA.

Conclusions

The frequency of positive anti-CD74 IgG antibodies was as high in patients with early axSpA as in those with late axSpA, with no significant differences. There was a significant difference in the frequency of positive anti-CD74 IgG antibodies between patients with positive and negative disease activity. Based on the sensitivity and specificity of anti-CD74 IgG, this is a promising diagnostic tool to support the clinical diagnosis of axSpA.
Conducting decoded neurofeedback studies
Authors: Taschereau-Dumouchel Vincent , Cortese Aurelio , Lau Hakwan , Kawato Mitsuo
Published: May 2020

Closed-loop neurofeedback has sparked great interest since its inception in the late 1960s. However, the field has historically faced various methodological challenges. Decoded fMRI neurofeedback may provide solutions to some of these problems. Notably, thanks to the recent advancements of machine learning approaches, it is now possible to target unconscious occurrences of specific multivoxel representations. In this tools of the trade paper, we discuss how to implement these interventions in rigorous double-blind placebo-controlled experiments. We aim to provide a step-by-step guide to address some of the most common methodological and analytical considerations. We also discuss tools that can be used to facilitate the implementation of new experiments. We hope that this will encourage more researchers to try out this powerful new intervention method.
Israel: trusts and succession
Authors: Kaplan Alon , Eyal Lyat , Liberman Meytal
Published: May 2020

The Israeli Foundation refers to the legal structure of an Israeli private trust, created in combination with an underlying company to hold the trust assets. This article will focus on this structure, as well as on the creation of the Israeli private trust by way of a deed (hekdesh) or by way of a contract. The article will continue by looking into the Israeli real estate trust, which is commonly created by a contract, and finally the article will explore the inheritance procedure in Israel and the issues arising from the conflict between the Trust Law, the Contracts Law, the Succession Law and the Gift Law.
Adult ICU Triage During the Coronavirus Disease 2019 Pandemic: Who Will Live and Who Will Die? Recommendations to Improve Survival*
Authors: Sprung Charles L. , Joynt Gavin M. , Christian Michael D. , Truog Robert D. , Rello Jordi , Nates Joseph L.
Published: May 2020

Objectives:

Coronavirus disease 2019 patients are currently overwhelming the world’s healthcare systems. This article provides practical guidance to front-line physicians forced to make critical rationing decisions.

Data Sources:

PubMed and Medline search for scientific literature, reviews, and guidance documents related to epidemic ICU triage including from professional bodies.

Study Selection:

Clinical studies, reviews, and guidelines were selected and reviewed by all authors and discussed by internet conference and email.

Data Extraction:

References and data were based on relevance and author consensus.

Data Synthesis:

We review key challenges of resource-driven triage and data from affected ICUs. We recommend that once available resources are maximally extended, triage is justified utilizing a strategy that provides the greatest good for the greatest number of patients. A triage algorithm based on clinical estimations of the incremental survival benefit (saving the most life-years) provided by ICU care is proposed. “First come, first served” is used to choose between individuals with equal priorities and benefits. The algorithm provides practical guidance, is easy to follow, rapidly implementable and flexible. It has four prioritization categories: performance score, ASA score, number of organ failures, and predicted survival. Individual units can readily adapt the algorithm to meet local requirements for the evolving pandemic. Although the algorithm improves consistency and provides practical and psychologic support to those performing triage, the final decision remains a clinical one. Depending on country and operational circumstances, triage decisions may be made by a triage team or individual doctors. However, an experienced critical care specialist physician should be ultimately responsible for the triage decision. Cautious discharge criteria are proposed acknowledging the difficulties to facilitate the admission of queuing patients.

Conclusions:

Individual institutions may use this guidance to develop prospective protocols that assist the implementation of triage decisions to ensure fairness, enhance consistency, and decrease provider moral distress.
Pharmacokinetic and pharmacodynamic evaluation of nano-fixed dose combination for hypertension
Authors: Pandey Avaneesh K. , Shafiq Nusrat , Bhandari Ritika K. , Rather Imraan I.G. , Kaur Navjot , Bhatia Alka , Sharma Sadhna , Malhotra Samir
Published: May 2020

Objective:

The current study was planned to formulate, characterize and evaluate the pharmacokinetics, and pharmacodynamics of a novel ‘NanoFDC’ comprising hydrochlorothiazide, candesartan (CNDT) and amlodipine.

Methodology:

The candidate drugs were loaded in poly(dl-lactide-co-glycolide) by emulsion–diffusion–evaporation method. The formulations were evaluated for their size, morphology, drug loading and in-vitro release individually. Repeat dose pharmacokinetic and pharmacodynamic study of the nano-fixed dose combination (FDC) was done in dexamethasone-induced animal model.

Results:

The entrapment efficiencies ranged from 44 ± 2.1, 32.2 ± 4 and 40.5 ± 2.6% for amlodipine, hydrochlorothiazide and CNDT, respectively. The nanoparticles ranged in size from 164 to 215 nm. In-vitro release profile of the nanoformulation showed unto 90% release by day 7 in simulated gastric fluid and simulated intestinal fluid, respectively. In pharmacokinetic analysis a sustained-release for 7 days was observed in nano-FDC group. Once weekly oral dosing of nano-FDC of amlodipine, CNDT and hydrochlorothiazide provided adequate antihypertensive effect which was not statistically different from daily dosing of free drugs in dexamethasone-induced animal model.

Conclusion:

Once weekly oral dosing of nano-FDC of amlodipine, CNDT and hydrochlorothiazide provided adequate antihypertensive effect and was not statistically different from daily dosing of free drugs in dexamethasone-induced animal model. This study provides proof of concept of feasibility of once weekly dosing of a nano-FDC comprising three antihypertensive drugs, which can lead to significant improvement in patient adherence to therapy.
New progress on the study of aortic stiffness in age-related hypertension
Authors: Onuh John O. , Qiu Hongyu
Published: May 2020

Hypertension is a worldwide known cause of morbidity and mortality in the elderly and is a major risk factor for cardiovascular complications such as stroke, myocardial infarction, renal complications and heart failure. Although the mechanisms of hypertension remain largely unknown, a recent new concept is that aortic stiffening is a cause of hypertension in middle-aged and older individuals, which highlighted the importance of aortic stiffening in the development of age-related hypertension. Understanding the pathogenesis of aortic stiffness therefore became one of the important approaches to preventing and controlling hypertension. This review discusses the recent progress of the potential causes of aortic stiffening and its implication on the pathogenesis of hypertension, in terms of aging, inflammation, metabolic syndromes, neuroendocrine and the interaction among these causes.
Bringing Radiation Exposures and Associated Health Risks into Perspective—Development of an App
Authors: Abend Michael , Stricklin Daniela , Flaig Nicole , Badie Christophe , Drouet Michel , Foster Crawford , Janiak Marek K. , Kuipers Tjerk , Lista Florigio , Nowosielska Ewa M. , Riccobono Diane , de Sanctis Stefania , Franchini Valeria , Tichy Ales , Port Matthias
Published: May 2020

The NATO HFM 291 research task group (RTG) on “Ionizing Radiation Bioeffects and Countermeasures” represents a group of scientists from military and civilian academic and scientific institutions primarily working in the field of radiobiology. Among other tasks, the RTG intends to extend their work on risk estimation and communication to bridge the gap in appropriate judgment of health risks given a certain radiation exposure. The group has no explicit psychological background but an expertise in radiobiology and risk assessment. The group believes that, as one of the essential first steps in risk communication, it is required to put radiation risk into perspective. Radiation risk requires a weight in comparison to already-known risks. What we envision is to Compare Radiation exposure-associated health Risks (CRRis App) with daily life health risks caused by other common exposures such as cigarette smoking, driving a car, etc. Within this paper, we provide (1) an overview of health risks after radiation exposure, (2) an explanation of the task and concept of an envisioned CRRis App, (3) an overview of existing software tools related to this issue, (4) a summary of inputs and discussions with experts in the field of radiation protection and risk communication during the ConRad conference, and finally, (5) identification of the next steps in the development of the App.
Cardiac donation after circulatory death
Authors: Iyer Arjun , Dhital Kumud
Published: May 2020

Purpose of review

Increasing number of patients with end-stage heart failure and those with improved survivorship from selective utilization of implantable mechanical circulatory support devices have added further burden and complexity to the transplant waitlist and on the rate-limiting availability of donor hearts from the standard pathway of donation after brain death. Unlike this conventional route, the increasing clinical use of donation after circulatory death (DCD) donor hearts necessitates a closer understanding of the logistics involved in the DCD process as well as of the risks associated with the unique pathophysiological consequences in this setting.

Recent findings

Notwithstanding a higher incidence of delayed graft function, the clinical utilization of DCD hearts for cardiac transplantation over the past five years has demonstrated this to be a well-tolerated and strategic alternative with excellent medium-term clinical outcomes.

The uptake of DCD heart transplantation remains selective and currently confined to Australia, the United Kingdom, Belgium, and more recently the USA. A more significant adoption will only come about through: a concerted effort to resolve the ethical and clinical controversies; a better understanding of postconditioning strategies; continued resolve to reduce the obligatory period of warm ischemia; and from better extracorporeal platforms that permit functional viability assessment of the DCD donor heart.
Environmental contamination with cytotoxic drugs in 15 hospitals from 11 European countries—results of the MASHA project
Authors: Korczowska Ewelina , Crul Mirjam , Tuerk Jochen , Meier Klaus
Published: May 2020

Background:

Evaluating environmental contamination with cytotoxic drugs in hospitals is one of the fundamental requirements to ensure the occupational safety of all healthcare professionals. The European Society of Oncology Pharmacy (ESOP) undertook the first independent, multicenter, pan-European study, involving over a dozen hospitals from 11 different countries, to measure the state of cytotoxic contamination in the workplace.

Objective:

To obtain an overview of the current situation in European hospitals with regards to cytotoxic drug contamination at various sites, including drug preparation (pharmacy) and administration areas (ward). The secondary objectives are to evaluate the environmental contamination with cytotoxic drugs circulating within a facility known as the hospital medication system (process flow of drug) and to evaluate the impact of changes in local cleaning practices.

Materials and methods:

The study was carried out at 15 hospitals in Europe evaluating the surface contamination in the preparation and administration areas before (part I) and after (part II and part III) training and the implementation of ESOP cleaning recommendations. Assessment of surface contamination with 11 antineoplastic drugs was performed using wipe samples taken from 10 comparable surfaces (5 each in the preparation and administration areas). These samples were analyzed by liquid chromatography–tandem mass spectrometry.

Results:

The study demonstrated the presence of surface contamination in preparation and administration areas in all hospitals, with measurable amounts of at least 1 agent detected on sampled surfaces. Before the implementation of the ESOP cleaning recommendations, 324 out of 1595 results were positive (20%). In 11 of 15 hospitals (73%), substances were detected which were not prepared or administrated in the sampling day. After implementation of the ESOP recommendations, only 14% of results were positive (226/1639). Sixty-nine percent of wards (9/13) improved or stayed at the same level in the number of positive samples. The floors on the wards were shown to be the most frequently contaminated (42% of samples were positive). The amount of contamination in the pharmacies was not correlated to the amount of chemotherapy prepared nor to the use of special devices such as closed-system transfer devices.

Conclusion:

The MASHA study provides an overview of the contamination levels with cytotoxic drugs in European hospitals. Upon implementation of ESOP cleaning recommendations, improvements could be seen, with a reduced number of positive-wipe samples and lower amounts of surface concentration detected. The study demonstrates that improving standard work procedures is able to substantially reduce contamination in the workplace.
Retrograde signals from endosymbiotic organelles: a common control principle in eukaryotic cells
Authors: Pfannschmidt Thomas , Terry Matthew J. , Van Aken Olivier , Quiros Pedro M.
Published: May 2020

Endosymbiotic organelles of eukaryotic cells, the plastids, including chloroplasts and mitochondria, are highly integrated into cellular signalling networks. In both heterotrophic and autotrophic organisms, plastids and/or mitochondria require extensive organelle-to-nucleus communication in order to establish a coordinated expression of their own genomes with the nuclear genome, which encodes the majority of the components of these organelles. This goal is achieved by the use of a variety of signals that inform the cell nucleus about the number and developmental status of the organelles and their reaction to changing external environments. Such signals have been identified in both photosynthetic and non-photosynthetic eukaryotes (known as retrograde signalling and retrograde response, respectively) and, therefore, appear to be universal mechanisms acting in eukaryotes of all kingdoms. In particular, chloroplasts and mitochondria both harbour crucial redox reactions that are the basis of eukaryotic life and are, therefore, especially susceptible to stress from the environment, which they signal to the rest of the cell. These signals are crucial for cell survival, lifespan and environmental adjustment, and regulate quality control and targeted degradation of dysfunctional organelles, metabolic adjustments, and developmental signalling, as well as induction of apoptosis. The functional similarities between retrograde signalling pathways in autotrophic and non-autotrophic organisms are striking, suggesting the existence of common principles in signalling mechanisms or similarities in their evolution. Here, we provide a survey for the newcomers to this field of research and discuss the importance of retrograde signalling in the context of eukaryotic evolution. Furthermore, we discuss commonalities and differences in retrograde signalling mechanisms and propose retrograde signalling as a general signalling mechanism in eukaryotic cells that will be also of interest for the specialist.

This article is part of the theme issue ‘Retrograde signalling from endosymbiotic organelles’.
The plastid transcription machinery and its coordination with the expression of nuclear genome: Plastid-Encoded Polymerase, Nuclear-Encoded Polymerase and the Genomes Uncoupled 1-mediated retrograde communication
Authors: Tadini Luca , Jeran Nicolaj , Peracchio Carlotta , Masiero Simona , Colombo Monica , Pesaresi Paolo
Published: May 2020

Plastid genes in higher plants are transcribed by at least two different RNA polymerases, the plastid-encoded RNA polymerase (PEP), a bacteria-like core enzyme whose subunits are encoded by plastid genes (
rpoA
,
rpoB
,
rpoC1
and
rpoC2
), and the nuclear-encoded plastid RNA polymerase (NEP), a monomeric bacteriophage-type RNA polymerase. Both PEP and NEP enzymes are active in non-green plastids and in chloroplasts at all developmental stages. Their transcriptional activity is affected by endogenous and exogenous factors and requires a strict coordination within the plastid and with the nuclear gene expression machinery. This review focuses on the different molecular mechanisms underlying chloroplast transcription regulation and its coordination with the photosynthesis-associated nuclear genes (
PhANGs
) expression. Particular attention is given to the link between NEP and PEP activity and the GUN1- (Genomes Uncoupled 1) mediated chloroplast-to-nucleus retrograde communication with respect to the
Δrpo
adaptive response, i.e. the increased accumulation of NEP-dependent transcripts upon depletion of PEP activity, and the editing-level changes observed in NEP-dependent transcripts, including
rpoB
and
rpoC1
, in
gun1
cotyledons after norflurazon or lincomycin treatment. The role of cytosolic preproteins and HSP90 chaperone as components of the GUN1-retrograde signalling pathway, when chloroplast biogenesis is inhibited in
Arabidopsis
cotyledons, is also discussed.

This article is part of the theme issue ‘Retrograde signalling from endosymbiotic organelles’.
Retrograde signalling in a virescent mutant triggers an anterograde delay of chloroplast biogenesis that requires GUN1 and is essential for survival
Authors: Loudya Naresh , Okunola Tolulope , He Jia , Jarvis Paul , López-Juez Enrique
Published: May 2020

Defects in chloroplast development are ‘retrograde-signalled’ to the nucleus, reducing synthesis of photosynthetic or related proteins. The
Arabidopsis
cue8
mutant manifests virescence, a slow-greening phenotype, and is defective at an early stage in plastid development. Greening cotyledons or early leaf cells of
cue8
exhibit immature chloroplasts which fail to fill the available cellular space. Such chloroplasts show reduced expression of genes of photosynthetic function, dependent on the plastid-encoded polymerase (PEP), while the expression of genes of housekeeping function driven by the nucleus-encoded polymerase (NEP) is elevated, a phenotype shared with mutants in plastid genetic functions. We attribute this phenotype to reduced expression of specific PEP-controlling sigma factors, elevated expression of
RPOT
(NEP) genes and maintained replication of plastid genomes (resulting in densely coalesced nucleoids in the mutant), i.e. it is due to an anterograde nucleus-to-chloroplast correction, analogous to retention of a juvenile plastid state. Mutants in plastid protein import components, particularly those involved in housekeeping protein import, also show this ‘retro-anterograde’ correction. Loss of CUE8 also causes changes in mRNA editing. The overall response has strong fitness value: loss of GUN1, an integrator of retrograde signalling, abolishes elements of it (albeit not others, including editing changes), causing bleaching and eventual seedling lethality upon
cue8 gun1
. This highlights the adaptive significance of virescence and retrograde signalling.

This article is part of the theme issue ‘Retrograde signalling from endosymbiotic organelles’.
Overexpression of chloroplast-targeted ferrochelatase 1 results in a
genomes uncoupled
chloroplast-to-nucleus retrograde signalling phenotype
Authors: Page Mike T. , Garcia-Becerra Tania , Smith Alison G. , Terry Matthew J.
Published: May 2020

Chloroplast development requires communication between the progenitor plastids and the nucleus, where most of the genes encoding chloroplast proteins reside. Retrograde signals from the chloroplast to the nucleus control the expression of many of these genes, but the signalling pathway is poorly understood. Tetrapyrroles have been strongly implicated as mediators of this signal with the current hypothesis being that haem produced by the activity of ferrochelatase 1 (FC1) is required to promote nuclear gene expression. We have tested this hypothesis by overexpressing FC1 and specifically targeting it to either chloroplasts or mitochondria, two possible locations for this enzyme. Our results show that targeting of FC1 to chloroplasts results in increased expression of the nuclear-encoded chloroplast genes
GUN4
,
CA1
,
HEMA1
,
LHCB2.1, CHLH
after treatment with Norflurazon (NF) and that this increase correlates to
FC1
gene expression and haem production measured by feedback inhibition of protochlorophyllide synthesis. Targeting FC1 to mitochondria did not enhance the expression of nuclear-encoded chloroplast genes after NF treatment. The overexpression of FC1 also increased nuclear gene expression in the absence of NF treatment, demonstrating that this pathway is operational in the absence of a stress treatment. Our results therefore support the hypothesis that haem synthesis is a promotive chloroplast-to-nucleus retrograde signal. However, not all FC1 overexpression lines enhanced nuclear gene expression, suggesting there is still a lot we do not understand about the role of FC1 in this signalling pathway.

This article is part of the theme issue ‘Retrograde signalling from endosymbiotic organelles’.
Thegenomes uncoupled-dependent signalling pathway coordinates plastid biogenesis with the synthesis of anthocyanins
Authors: Richter Andreas S. , Tohge Takayuki , Fernie Alisdair R. , Grimm Bernhard
Published: May 2020

In recent years, it has become evident that plants perceive, integrate and communicate abiotic stress signals through chloroplasts. During the process of acclimation plastid-derived, retrograde signals control nuclear gene expression in response to developmental and environmental cues leading to complex genetic and metabolic reprogramming to preserve cellular homeostasis under challenging environmental conditions. Upon stress-induced dysfunction of chloroplasts, GENOMES UNCOUPLED (GUN) proteins participate in the repression ofPHOTOSYNTHESIS-ASSOCIATED NUCLEAR GENES(PHANGs). Here, we show that the retrograde signal emitted by, or communicated through, GUN-proteins is also essential to induce the accumulation of photoprotective anthocyanin pigments when chloroplast development is attenuated. Comparative whole transcriptome sequencing and genetic analysis reveal GUN1 and GUN5-dependent signals as a source for the regulation of genes involved in anthocyanin biosynthesis. The signal transduction cascade includes well-known transcription factors for the control of anthocyanin biosynthesis, which are deregulated ingunmutants. We propose that regulation ofPHANGsand genes contributing to anthocyanin biosynthesis are two, albeit oppositely, co-regulated processes during plastid biogenesis.

This article is part of the theme issue ‘Retrograde signalling from endosymbiotic organelles’.
Is there a role for tau glutathione transferases in tetrapyrrole metabolism and retrograde signalling in plants?
Authors: Sylvestre-Gonon Elodie , Schwartz Mathieu , Girardet Jean-Michel , Hecker Arnaud , Rouhier Nicolas
Published: May 2020

In plants, tetrapyrrole biosynthesis occurs in chloroplasts, the reactions being catalysed by stromal and membrane-bound enzymes. The tetrapyrrole moiety is a backbone for chlorophylls and cofactors such as sirohaems, haems and phytochromobilins. Owing to this diversity, the potential cytotoxicity of some precursors and the associated synthesis costs, a tight control exists to adjust the demand and the fluxes for each molecule. After synthesis, haems and phytochromobilins are incorporated into proteins found in other subcellular compartments. However, there is only very limited information about the chaperones and membrane transporters involved in the trafficking of these molecules. After summarizing evidence indicating that glutathione transferases (GST) may be part of the transport and/or degradation processes of porphyrin derivatives, we provide experimental data indicating that tau glutathione transferases (GSTU) bind protoporphyrin IX and haem moieties and use structural modelling to identify possible residues responsible for their binding in the active site hydrophobic pocket. Finally, we discuss the possible roles associated with the binding, catalytic transformation (i.e. glutathione conjugation) and/or transport of tetrapyrroles by GSTUs, considering their subcellular localization and capacity to interact with ABC transporters.

This article is part of the theme issue ‘Retrograde signalling from endosymbiotic organelles’.
Spatial chloroplast-to-nucleus signalling involving plastid–nuclear complexes and stromules
Authors: Mullineaux Philip M. , Exposito-Rodriguez Marino , Laissue Pierre Philippe , Smirnoff Nicholas , Park Eunsook
Published: May 2020

Communication between chloroplasts and the nucleus in response to various environmental cues may be mediated by various small molecules. Signalling specificity could be enhanced if the physical contact between these organelles facilitates direct transfer and prevents interference from other subcellular sources of the same molecules. Plant cells have plastid–nuclear complexes, which provide close physical contact between these organelles. Plastid-nuclear complexes have been proposed to facilitate transfer of photosynthesis-derived H
2
O
2
to the nucleus in high light. Stromules (stroma filled tubular plastid extensions) may provide an additional conduit for transfer of a wider range of signalling molecules, including proteins. However, plastid–nuclear complexes and stromules have been hitherto treated as distinct phenomena. We suggest that plastid–nuclear complexes and stromules work in a coordinated manner so that, according to environmental conditions or developmental state, the two modes of connection contribute to varying extents. We hypothesize that this association is dynamic and that there may be a link between plastid–nuclear complexes and the development of stromules. Furthermore, the changes in contact could alter signalling specificity by allowing an extended or different range of signalling molecules to be delivered to the nucleus.

This article is part of the theme issue ‘Retrograde signalling from endosymbiotic organelles’.
Photosynthetic signalling during high light stress and recovery: targets and dynamics
Authors: Gollan Peter J. , Aro Eva-Mari
Published: May 2020

The photosynthetic apparatus is one of the major primary sensors of the plant's external environment. Changes in environmental conditions affect the balance between harvested light energy and the capacity to deal with excited electrons in the stroma, which alters the redox homeostasis of the photosynthetic electron transport chain. Disturbances to redox balance activate photosynthetic regulation mechanisms and trigger signalling cascades that can modify the transcription of nuclear genes. H
2
O
2
and oxylipins have been identified as especially prominent regulators of gene expression in response to excess light stress. This paper explores the hypothesis that photosynthetic imbalance triggers specific signals that target discrete gene profiles and biological processes. Analysis of the major retrograde signalling pathways engaged during high light stress and recovery demonstrates both specificity and overlap in gene targets. This work reveals distinct, time-resolved profiles of gene expression that suggest a regulatory interaction between rapidly activated abiotic stress response and induction of secondary metabolism and detoxification processes during recovery. The findings of this study show that photosynthetic electron transport provides a finely tuned sensor for detecting and responding to the environment through chloroplast retrograde signalling.

This article is part of the theme issue ‘Retrograde signalling from endosymbiotic organelles’
Chloroplast-to-nucleus retrograde signalling controls intercellular trafficking via plasmodesmata formation
Authors: Ganusova Elena E. , Reagan Brandon C. , Fernandez Jessica C. , Azim Mohammad F. , Sankoh Amie F. , Freeman Kyle M. , McCray Tyra N. , Patterson Kelsey , Kim Chinkee , Burch-Smith Tessa M.
Published: May 2020

The signalling pathways that regulate intercellular trafficking via plasmodesmata (PD) remain largely unknown. Analyses of mutants with defects in intercellular trafficking led to the hypothesis that chloroplasts are important for controlling PD, probably by retrograde signalling to the nucleus to regulate expression of genes that influence PD formation and function, an idea encapsulated in the organelle-nucleus-PD signalling (ONPS) hypothesis. ONPS is supported by findings that point to chloroplast redox state as also modulating PD. Here, we have attempted to further elucidate details of ONPS. Through reverse genetics, expression of select nucleus-encoded genes with known or predicted roles in chloroplast gene expression was knocked down, and the effects on intercellular trafficking were then assessed. Silencing most genes resulted in chlorosis, and the expression of several photosynthesis and tetrapyrrole biosynthesis associated nuclear genes was repressed in all silenced plants. PD-mediated intercellular trafficking was changed in the silenced plants, consistent with predictions of the ONPS hypothesis. One striking observation, best exemplified by silencing thePNPasehomologues, was that the degree of chlorosis of silenced leaves was not correlated with the capacity for intercellular trafficking. Finally, we measured the distribution of PD in silenced leaves and found that intercellular trafficking was positively correlated with the numbers of PD. Together, these results not only provide further support for ONPS but also point to a genetic mechanism for PD formation, clarifying a longstanding question about PD and intercellular trafficking.

This article is part of the theme issue ‘Retrograde signalling from endosymbiotic organelles'.
Linking mitochondrial and chloroplast retrograde signalling in plants
Authors: Wang Yan , Selinski Jennifer , Mao Chunli , Zhu Yanqiao , Berkowitz Oliver , Whelan James
Published: May 2020

Retrograde signalling refers to the regulation of nuclear gene expression in response to functional changes in organelles. In plants, the two energy-converting organelles, mitochondria and chloroplasts, are tightly coordinated to balance their activities. Although our understanding of components involved in retrograde signalling has greatly increased in the last decade, studies on the regulation of the two organelle signalling pathways have been largely independent. Thus, the mechanism of how mitochondrial and chloroplastic retrograde signals are integrated is largely unknown. Here, we summarize recent findings on the function of mitochondrial signalling components and their links to chloroplast retrograde responses. From this, a picture emerges showing that the major regulators are integrators of both organellar retrograde signalling pathways.

This article is part of the theme issue ‘Retrograde signalling from endosymbiotic organelles’.
The transcription factor ANAC017 is a key regulator of mitochondrial proteotoxic stress responses in plants
Authors: Kacprzak Sylwia M. , Dahlqvist Anton , Van Aken Olivier
Published: May 2020

Impaired mitochondrial translation or reduced mitochondrial protein import can lead to imbalances in mitochondrial protein composition. Such mitochondrial proteotoxic stresses can trigger a nuclear transcriptional response commonly described as the mitochondrial unfolded protein response (UPR
mt
). Despite extensive studies of UPR
mt
pathways in animal and fungal systems, very little is known about how the UPR
mt
is regulated in plants. Through comparison of
Arabidopsis thaliana
whole-genome transcriptome data, it was found that most genes induced by mitochondrial ribosome inhibitor doxycycline are also induced by Complex III inhibitor antimycin A. We demonstrate that transcriptional responses to a wide range of mitochondrial proteotoxic stress-triggers are regulated by the transcription factor ANAC017, which was shown to reside in the endoplasmic reticulum (ER). By contrast, no consistent evidence was found for genes that are specifically induced by doxycycline but not antimycin A. Furthermore, ANAC017 gain- and loss-of-function mutants showed marked resistance or susceptibility, respectively, to mitochondrial stress-inducing treatments, demonstrating the physiological importance of ANAC017 during mitochondrial proteotoxic stress. Finally, it was shown that ethylene signalling promotes mitochondria-to-nucleus signalling, most likely independently of ANAC017. Overall, this study shows that in plants, the UPR
mt
is largely overlapping with, and perhaps identical to, ‘classical’ mitochondrial retrograde signalling, and is mediated by ER-anchored transcription factor ANAC017.

This article is part of the theme issue ‘Retrograde signalling from endosymbiotic organelles’.
Dissecting the interaction of photosynthetic electron transfer with mitochondrial signalling and hypoxic response in the Arabidopsis
rcd1
mutant
Authors: Shapiguzov Alexey , Nikkanen Lauri , Fitzpatrick Duncan , Vainonen Julia P. , Gossens Richard , Alseekh Saleh , Aarabi Fayezeh , Tiwari Arjun , Blokhina Olga , Panzarová Klára , Benedikty Zuzana , Tyystjärvi Esa , Fernie Alisdair R. , Trtílek Martin , Aro Eva-Mari , Rintamäki Eevi , Kangasjärvi Jaakko
Published: May 2020

The Arabidopsis mutant
rcd1
is tolerant to methyl viologen (MV). MV enhances the Mehler reaction, i.e. electron transfer from Photosystem I (PSI) to O
2
, generating reactive oxygen species (ROS) in the chloroplast. To study the MV tolerance of
rcd1
, we first addressed chloroplast thiol redox enzymes potentially implicated in ROS scavenging. NADPH-thioredoxin oxidoreductase type C (NTRC) was more reduced in
rcd1
. NTRC contributed to the photosynthetic and metabolic phenotypes of
rcd1
, but did not determine its MV tolerance. We next tested
rcd1
for alterations in the Mehler reaction. In
rcd1
, but not in the wild type, the PSI-to-MV electron transfer was abolished by hypoxic atmosphere. A characteristic feature of
rcd1
is constitutive expression of mitochondrial dysfunction stimulon (MDS) genes that affect mitochondrial respiration. Similarly to
rcd1
, in other MDS-overexpressing plants hypoxia also inhibited the PSI-to-MV electron transfer. One possible explanation is that the MDS gene products may affect the Mehler reaction by altering the availability of O
2
. In green tissues, this putative effect is masked by photosynthetic O
2
evolution. However, O
2
evolution was rapidly suppressed in MV-treated plants. Transcriptomic meta-analysis indicated that MDS gene expression is linked to hypoxic response not only under MV, but also in standard growth conditions.

This article is part of the theme issue ‘Retrograde signalling from endosymbiotic organelles’.
Mitochondrial cross-compartmental signalling to maintain proteostasis and longevity
Authors: Molenaars Marte , Daniels Eileen G. , Meurs Amber , Janssens Georges E. , Houtkooper Riekelt H.
Published: May 2020

Lifespan in eukaryotic species can be prolonged by shifting from cellular states favouring growth to those favouring maintenance and stress resistance. For instance, perturbations in mitochondrial oxidative phosphorylation (OXPHOS) can shift cells into this latter state and extend lifespan. Because mitochondria rely on proteins synthesized from nuclear as well as mitochondrial DNA, they need to constantly send and receive messages from other compartments of the cell in order to function properly and maintain homeostasis, and lifespan extension is often dependent on this cross-compartmental signalling. Here, we describe the mechanisms of bi-directional mitochondrial cross-compartmental signalling resulting in proteostasis and longevity. These proteostasis mechanisms are highly context-dependent, governed by the origin and extent of stress. Furthermore, we discuss the translatability of these mechanisms and explore therapeutic developments, such as the antibiotic studies targeting mitochondria or mitochondria-derived peptides as therapies for age-related diseases such as neurodegeneration and cancer.

This article is part of the theme issue ‘Retrograde signalling from endosymbiotic organelles’.
Chloroplast-associated molecular patterns as concept for fine-tuned operational retrograde signalling
Authors: Unal Dilek , García-Caparrós Pedro , Kumar Vijay , Dietz Karl-Josef
Published: May 2020

Chloroplasts compose about one-quarter of the mesophyll cell volume and contain about 60% of the cell protein. Photosynthetic carbon assimilation is the dominating metabolism in illuminated leaves. To optimize the resource expenditure in these costly organelles and to control and adjust chloroplast metabolism, an intensive transfer of information between nucleus–cytoplasm and chloroplasts occurs in both directions as anterograde and retrograde signalling. Recent research identified multiple retrograde pathways that use metabolite transfer and include reaction products of lipids and carotenoids with reactive oxygen species (ROS). Other pathways use metabolites of carbon, sulfur and nitrogen metabolism, low molecular weight antioxidants and hormone precursors to carry information between the cell compartments. This review focuses on redox- and ROS-related retrograde signalling pathways. In analogy to the microbe-associated molecular pattern, we propose the term ‘chloroplast-associated molecular pattern' which connects chloroplast performance to extrachloroplast processes such as nuclear gene transcription, posttranscriptional processing, including translation, and RNA and protein fate.

This article is part of the theme issue ‘Retrograde signalling from endosymbiotic organelles'.
Retrograde signals from mitochondria reprogramme skoto-morphogenesis in
Arabidopsis thaliana
via alternative oxidase 1a
Authors: Merendino Livia , Courtois Florence , Grübler Björn , Bastien Olivier , Straetmanns Vera , Chevalier Fabien , Lerbs-Mache Silva , Lurin Claire , Pfannschmidt Thomas
Published: May 2020

The early steps in germination and development of angiosperm seedlings often occur in the dark, inducing a special developmental programme called skoto-morphogenesis. Under these conditions photosynthesis cannot work and all energetic requirements must be fulfilled by mitochondrial metabolization of storage energies. Here, we report the physiological impact of mitochondrial dysfunctions on the skoto-morphogenic programme by using the
Arabidopsis rpoTmp
mutant. This mutant is defective in the T7-phage-type organellar RNA polymerase shared by plastids and mitochondria. Lack of this enzyme causes a mitochondrial dysfunction resulting in a strongly reduced mitochondrial respiratory chain and a compensatory upregulation of the alternative-oxidase (AOX)-dependent respiration. Surprisingly, the mutant exhibits a triple-response-like phenotype with a twisted apical hook and a shortened hypocotyl. Highly similar phenotypes were detected in other respiration mutants (
rug3
and
atphb3)
and in WT seedlings treated with the respiration inhibitor KCN. Further genetic and molecular data suggest that the observed skoto-morphogenic alterations are specifically dependent on the activity of the AOX1a enzyme. Microarray analyses indicated that a retrograde signal from mitochondria activates the ANAC017-dependent pathway which controls the activation of
AOX1A
transcription. In sum, our analysis identifies AOX as a functional link that couples the formation of a triple-response-like phenotype to mitochondrial dysfunction.

This article is part of the theme issue ‘Retrograde signalling from endosymbiotic organelles'.