Observing the inner parsec-scale region of candidate neutrino-emitting blazars

Context. Many questions concerning the nature of astrophysical counterparts of high-energy neutrinos remain unanswered. There is increasing evidence of a connection between blazar jets and neutrino events, with the flare of the γ-ray blazar TXS 0506+056 in spatial and temporal proximity of IC 170922A representing one of the most outstanding associations of high-energy neutrinos with astrophysical sources reported so far. Aims. With the purpose of characterising potential blazar counterparts to high-energy neutrinos, we analysed the parsec-scale regions of γ-ray blazars in spatial coincidence with high-energy neutrinos, detected by the IceCube Observatory. Specifically, we intended to investigate peculiar radio properties of the candidate counterparts related to the neutrino production, such as radio flares coincident with the neutrino detection or features in jet morphology (limb brightening, transverse structures). Methods. We collected multi-frequency, very-long-baseline interferometry (VLBI) follow-up observations of candidate counterparts of four high-energy neutrino events detected by IceCube between January 2019 and November 2020, with a focus on γ-ray-associated objects. We analysed their radio characteristics soon after the neutrino arrival in comparison with archival VLBI observations and low-frequency radio observations. We discussed our results with respect to previous statistical works and studies on the case of TXS 0506+056. Results. We identified and analysed five potential neutrino-emitting blazars in detail. Our results suggest an enhanced state of activity for one source, PKS 1725+123. However, the lack of adequate monitoring prior to the neutrino events was a limitation in tracing radio activity and morphological changes in all the sources. Conclusions. We suggest that PKS 1725+123 is a promising neutrino source candidate. For the other sources, our results alone do not reveal a strong connection between the radio activity state at the neutrino arrival. A larger number of VLBI and multi-wavelength follow-up observations of neutrino events are now essential to our understanding of the neutrino production mechanisms in astrophysical sources.© ESO 2022.We thank the referee for her/his useful suggestions. J.M. and MPT acknowledge financial support from the State Agency for Research of the Spanish MCIU through the “Center of Excellence Severo Ochoa” award to the Instituto de Astrofísica de Andalucía (SEV-2017-0709) and through grants RTI2018-096228-B-C31 and PID2020-117404GB-C21 (MICIU/FEDER, EU). S.B. acknowledges financial support by the European Research Council for the ERC Starting grant MessMapp, under contract no. 949555. B.W.S. is grateful for the support by the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (MSIT) of Korea (NRF-2020K1A3A1A78114060). We thank to L. Petrov for granting permission for using data from the Astrogeo VLBI FITS image database. The European VLBI Network is a joint facility of independent European, African, Asian, and North American radio astronomy institutes. Scientific results from data presented in this publication are derived from the following EVN project codes: RG011, EG108. The National Radio Astronomy Observatory is a facility of the National Science Foundation operated under cooperative agreement by Associated Universities, Inc. This work made use of the Swinburne University of Technology software correlator, developed as part of the Australian Major National Research Facilities Programme and operated under licence. e-MERLIN is a National Facility operated by the University of Manchester at Jodrell Bank Observatory on behalf of STFC. This research has made use of data from the MOJAVE database that is maintained by the MOJAVE team (Lister et al. 2018). This research has made use of the CIRADA cutout service at URL cutouts.cirada.ca, operated by the Canadian Initiative for Radio Astronomy Data Analysis (CIRADA). CIRADA is funded by a grant from the Canada Foundation for Innovation 2017 Innovation Fund (Project 35999), as well as by the Provinces of Ontario, British Columbia, Alberta, Manitoba and Quebec, in collaboration with the National Research Council of Canada, the US National Radio Astronomy Observatory and Australia’s Commonwealth Scientific and Industrial Research Organisation. This research has made use of the NASA/IPAC Extragalactic Database (NED), which is operated by the Jet Propulsion Laboratory, California Institute of Technology, under contract with the National Aeronautics and Space Administration.Peer reviewe

Promoter-driven splicing regulation in fission yeast

The meiotic cell cycle is modified from the mitotic cell cycle by having a premeiotic S phase which leads to high levels of recombination, two rounds of nuclear division with no intervening DNA synthesis, and a reductional pattern of chromosome segregation. Rem1 is a cyclin that is expressed only during meiosis in the fission yeast Schizosaccharomyces pombe. Cells in which rem1 has been deleted show a decreased intragenic meiotic recombination and a delay at the onset of meiosis I. When ectopically expressed in mitotically growing cells, Rem1 induces a G1 arrest followed by severe mitotic catastrophes. Here we show that rem1 expression is regulated at the level of both transcription and splicing, encoding for two proteins with different function depending on the intron retention. We have determined that the regulation of rem1 splicing is not dependent on any transcribed region of the gene. Furthermore, when the rem1 promoter is fused to other intron-containing genes, the chimeras show a meiotic-specific regulation of splicing, exactly as endogenous rem1. This regulation is dependent on two transcription factors of the forkhead family, Mei4 and Fkh2. While Mei4 induces both transcription and splicing of rem1, Fkh2 is responsible for the intron retention of the transcript during vegetative growth and pre-meiotic S phase.El ciclo meiótico se diferencia del ciclo mitótico por tener una fase S pre-meiótica caracterizada por altos niveles de recombinación, dos rondas de división nuclear sin síntesis de DNA entre las dos y una segregación cromosómica reduccional. Rem1 es una ciclina que sólo se expresa en meiosis en la levadura de fisión Schizosaccharomyces pombe. Celulas con rem1 deleccionado presentan una tasa de recombinación intragénica disminuida y un retraso en el inicio de meiosis I. Cuando se expresa ectópicamente en células creciendo vegetativamente, Rem1 induce un arresto en G1 seguido de catástrofe mitótica. Este trabajo describe que la expresión de rem1 está regulada a nivel de la trascripción y el procesamiento, codificando para dos proteínas con funciones diferentes dependiendo de la retención intrónica.. Hemos determinado que la regulación del splicing de rem1 no depende de ninguna región transcrita del gen. Además, cuando el promotor se fusiona a otros genes que contienen intrones, las quimeras presentan una regulación específica de meiosis como el rem1 endógeno. Esta regulación depende de dos factores de transcripción de la familia Forkhead, Mei4 y Fkh2. Mientras Mei4 induce la transcripción y el splicing de rem1, Fkh2 es responsable de la retención intrónica del tránscrito durante crecimiento vegetativo y fase S pre-meiótica

A Meiosis-Specific Cyclin Regulated by Splicing Is Required for Proper Progression through Meiosis

The meiotic cell cycle is modified from the mitotic cell cycle by having a premeiotic S phase which leads to high levels of recombination, a reductional pattern of chromosome segregation at the first division, and a second division with no intervening DNA synthesis. Cyclin-dependent kinases are essential for progression through the meiotic cell cycle, as for the mitotic cycle. Here we show that a fission yeast cyclin, Rem1, is present only during meiosis. Cells lacking Rem1 have impaired meiotic recombination, and Rem1 is required for premeiotic DNA synthesis when Cig2 is not present. rem1 expression is regulated at the level of both transcription and splicing, with Mei4 as a positive and Cig2 a negative factor of rem1 splicing. This regulation ensures the timely appearance of the different cyclins during meiosis, which is required for the proper progression through the meiotic cell cycle. We propose that the meiosis-specific B-type cyclin Rem1 has a central role in bringing about progression through meiosis

The peroxiredoxin Tpx1 is essential as a H202-scavenger during aerobic growth in fission yeast

Peroxiredoxins are known to interact with hydrogen peroxide (H2O2) and to participate in oxidant scavenging, redox signal transduction, and heat-shock responses. The two-cysteine peroxiredoxin Tpx1 of Schizosaccharomyces pombe has been characterized as the H2O2 sensor that transduces the redox signal to the transcription factor Pap1. Here, we show that Tpx1 is essential for aerobic, but not anaerobic, growth. We demonstrate that Tpx1 has an exquisite sensitivity for its substrate, which explains its participation in maintaining low steady-state levels of H2O2. We also show in vitro and in vivo that inactivation of Tpx1 by oxidation of its catalytic cysteine to a sulfinic acid is always preceded by a sulfinic acid form in a covalently linked dimer, which may be important for understanding the kinetics of Tpx1 inactivation. Furthermore, we provide evidence that a strain expressing Tpx1.C169S, lacking the resolving cysteine, can sustain aerobic growth, and we show that small reductants can modulate the activity of the mutant protein in vitro, probably by supplying a thiol group to substitute for cysteine 169

Activation of Srk1 by the Mitogen-activated Protein Kinase Sty1/Spc1 Precedes Its Dissociation from the Kinase and Signals Its Degradation

Control of cell cycle progression by stress-activated protein kinases (SAPKs) is essential for cell adaptation to extracellular stimuli. The Schizosaccharomyces pombe SAPK Sty1/Spc1 orchestrates general changes in gene expression in response to diverse forms of cytotoxic stress. Here we show that Sty1/Spc1 is bound to its target, the Srk1 kinase, when the signaling pathway is inactive. In response to stress, Sty1/Spc1 phosphorylates Srk1 at threonine 463 of the regulatory domain, inducing both activation of Srk1 kinase, which negatively regulates cell cycle progression by inhibiting Cdc25, and dissociation of Srk1 from the SAPK, which leads to Srk1 degradation by the proteasome

The peroxiredoxin Tpx1 is essential as a H202-scavenger during aerobic growth in fission yeast

Peroxiredoxins are known to interact with hydrogen peroxide (H2O2) and to participate in oxidant scavenging, redox signal transduction, and heat-shock responses. The two-cysteine peroxiredoxin Tpx1 of Schizosaccharomyces pombe has been characterized as the H2O2 sensor that transduces the redox signal to the transcription factor Pap1. Here, we show that Tpx1 is essential for aerobic, but not anaerobic, growth. We demonstrate that Tpx1 has an exquisite sensitivity for its substrate, which explains its participation in maintaining low steady-state levels of H2O2. We also show in vitro and in vivo that inactivation of Tpx1 by oxidation of its catalytic cysteine to a sulfinic acid is always preceded by a sulfinic acid form in a covalently linked dimer, which may be important for understanding the kinetics of Tpx1 inactivation. Furthermore, we provide evidence that a strain expressing Tpx1.C169S, lacking the resolving cysteine, can sustain aerobic growth, and we show that small reductants can modulate the activity of the mutant protein in vitro, probably by supplying a thiol group to substitute for cysteine 169

Spatiotemporal control of forkhead binding to DNA regulates the meiotic gene expression program

Meiosis is a differentiated program of the cell cycle that is characterized by high levels of recombination followed by two nuclear divisions. In fission yeast, the genetic program during meiosis is regulated at multiple levels, including transcription, mRNA stabilization, and splicing. Mei4 is a forkhead transcription factor that controls the expression of mid-meiotic genes. Here, we describe that Fkh2, another forkhead transcription factor that is essential for mitotic cell-cycle progression, also plays a pivotal role in the control of meiosis. Fkh2 binding preexists in most Mei4-dependent genes, inhibiting their expression. During meiosis, Fkh2 is phosphorylated in a CDK/Cig2-dependent manner, decreasing its affinity for DNA, which creates a window of opportunity for Mei4 binding to its target genes. We propose that Fkh2 serves as a placeholder until the later appearance of Mei4 with a higher affinity for DNA that induces the expression of a subset of meiotic genes.This work was supported by grants from the Spanish Ministerio de Economia y Competitividad (MINECO) (grants BFU2012-31939 and BFU2015-66347), PLAN E, and Feder. E.H. is a recipient of an ICREA Academia Award (Generalitat de Catalunya)