bluuebunny/crossref_metadata_2025 huggingface dataset:
Resolved views on early galaxy evolution
Authors: Wuyts Stijn , Förster Schreiber Natascha M.
Published: June 2020

Resolved observations of star-forming galaxies at cosmic noon with the Hubble Space Telescope and large ground-based facilities provide a view on the spatial distribution of stars, gas and dust, and probe gaseous motions revealing the central gravitational potential and local feedback processes at play. In this paper, we review recent insights gained from such observations, with an emphasis on results obtained through optical/near-infrared imaging and imaging spectroscopy. Their context and implications are documented more fully in a forthcoming review article by Förster Schreiber & Wuyts (in prep).
Nature and physical properties of gas-mass selected galaxies using integral field spectroscopy
Authors: Boogaard Leindert A.
Published: June 2020

Mapping the molecular gas content of the universe is key to our understanding of the build-up of galaxies over cosmic time. Spectral line scans in deep fields, such as the Hubble Ultra Deep Field (HUDF), provide a unique view on the cold gas content out to high redshift. By conducting ‘spectroscopy-of-everything’, these flux-limited observations are sensitive to the molecular gas in galaxies without preselection, revealing the cold gas content of galaxies that would not be selected in traditional studies.

In order to capitalize on the molecular gas observations, knowledge about the physical conditions of the galaxies detected in molecular gas, such as their interstellar medium conditions, is key. Fortunately, deep surveys with integral-field spectrographs are providing an unprecedented view of the galaxy population, providing redshifts and measurements of restframe UV/optical lines for thousands of galaxies.

We present the results from the synergy between the ALMA Spectroscopic Survey of the HUDF (ASPECS), with deep integral field spectroscopy from the MUSE HUDF survey and multi-wavelength data. We discuss the nature of the galaxies detected in molecular gas without preselection and their physical properties, such as star formation rate and metallicity. We show how the combination of ALMA and MUSE integral field spectroscopy can constrain the physical properties in galaxies located around the main sequence during the peak of galaxy formation.
Molecular clouds in a Milky Way progenitor at z = 1
Authors: Dessauges-Zavadsky Miroslava , Richard Johan , Combes Françoise , Schaerer Daniel , Rujopakarn Wiphu , Mayer Lucio
Published: June 2020

Thanks to the remarkable ALMA capabilities and the unique configuration of the Cosmic Snake galaxy behind a massive galaxy cluster, we could resolve molecular clouds down to 30 pc linear physical scales in a typical Milky Way progenitor at z = 1.036, through CO(4–3) observations performed at the ∼ 0.2″ angular resolution. We identified 17 individual giant molecular clouds. These high-redshift molecular clouds are clearly different from their local analogues, with 10–100 times higher masses, densities, and internal turbulence. They are offset from the Larson scaling relations. We argue that the molecular cloud physical properties are dependent on the ambient interstellar conditions particular to the host galaxy. We find these high-redshift clouds in virial equilibrium, and derive, for the first time, the CO-to-H2 conversion factor from the kinematics of independent molecular clouds at z = 1. The measured large clouds gas masses demonstrate the existence of parent gas clouds with masses high enough to allow the in-situ formation of similarly massive stellar clumps seen in the Cosmic Snake galaxy in comparable numbers. Our results support the formation of molecular clouds by fragmentation of turbulent galactic gas disks, which then become the stellar clumps observed in distant galaxies.
ALMA witnesses the assembly of first galaxies
Authors: Carniani Stefano
Published: June 2020

Characterising primeval galaxies entails the challenging goal of observing galaxies with modest star formation rates (SFR < 100 Mȯyr−1) and approaching the beginning of the reionisation epoch (z > 6). To date a large number of primeval galaxies have been identified thanks to deep near-infrared surveys. However, to further our understanding on the formation and evolution of such primeval objects, we must investigate their nature and physical properties through multi-band spectroscopic observations. Information on dust content, metallicity, interactions with the surrounding environment, and outflows can be obtained with ALMA observations of far-infrared (FIR) lines such as the [Cii] at 158 μm and [Oiii] at 88 μm. Here, we, thus, discuss the recent results unveiled by ALMA observations and present new [Cii] observations of BDF-3299, a star-forming galaxy at z = 7.1 showing a spatial and spectral offset between the rest-frame UV and the FIR lines emission.
Preliminary results from prebiotic molecules with ALMA in the era of artificial intelligence
Authors: Villicana-Pedraza I. , Walterbos R. , Carreto-Parra F. , Ott. J. , Momjian E. , Thelen A. , Ginsburg A. , Zapata L. , Gonzalez M. , Floyd J. , Saucedo J. , Binette L. , Prugh S.
Published: June 2020

Study of the composition from diverse sources of the Universe helps to us to understand their evolution. Molecular spectroscopy provides detailed information of the observed objects. We present a small study of the starburst NGC 253 with ALMA at 1mm. We detect the prebiotic molecules NH2CHO, and CNCHO. We obtain the integrated intensity maps and abundances of HNCO, CH3OH, H3O+ and CH3C2H. We propose the use of Artificial Intelligence for big data to find prebiotic molecules in galaxies.
Spectroscopy with the JWST Advanced Deep Extragalactic Survey (JADES) - the NIRSpec/NIRCAM GTO galaxy evolution project
Authors: Bunker Andrew J.
Published: June 2020

I present an overview of the JWST Advanced Deep Extragalactic Survey (JADES), a joint program of the JWST/NIRCam and NIRSpec Guaranteed Time Observations (GTO) teams involving 950 hours of observation. We will target two well-studied fields with excellent supporting data (e.g., from HST-CANDELS): GOODS-North and South, including the Ultra Deep Field. The science goal of JADES is to chart galaxy evolution at z > 2, and potentially out to z > 10, using the rest-frame optical and near-IR though observations from ≍ 1–5μm. Multi-colour NIRCam imaging with 9 filters will enable photometric redshifts and the application of the Lyman break technique out to unprecedented distances. NIRSpec spectroscopy (with spectral resolving powers of R = 100, 1000 & 2700) will measure secure spectroscopic redshifts of the photometrically-selected population, as well as stellar continuum slopes in the UV rest-frame, and hence study the role of dust, stellar population age, and other effects. Measuring emission lines can constrain the dust extinction, star formation rates, metallicity, chemical abundances, ionization and excitation mechanism in high redshift galaxies. Coupling NIRCam and NIRSpec observations will determine stellar populations (age, star formation histories, abundances) of galaxies and provide the information to correct their broad-band spectral energy distribution for likely line contamination. Potentially we can search for signatures of Population III stars such as HeII. We can address the contribution of star-forming galaxies at z > 7 to reionization by determining the faint end slope of the luminosity function and investigating the escape fraction of ionizing photons by comparing the UV stellar continuum with the Balmer-line fluxes.
The molecular gas content in a protocluster at z = 17: Star formation and AGN feedback
Authors: D’Amato Q. , Prandoni I. , Gilli R. , Massardi M. , Liuzzo E. , Mignoli M. , Vignali C. , Peca A. , Nanni R.
Published: June 2020

A large-scale structure has been recently discovered at z = 1.7, around a powerful FRII radio galaxy. Eight Star Forming Galaxies (SFGs) have been discovered within Δ z ≍ 0.0095 and at < 1 Mpc from the FRII, indicating that this is a signpost of a protocluster. Furthermore, a significant X-ray diffuse emission overlapping the Eastern lobe of the FRII has been detected. Protoclusters are the ideal targets to investigate the complex assembly processes leading to the formation of local galaxy clusters. We will exploit new ALMA CO(2-1) observations (PI: R. Gilli) of the entire region around the FRII galaxy to trace the molecular gas content, in order to discover new protocluster members. Coupling these measurements with the multi-wavelength data coverage available for this field, we aim at placing constrains on the physical conditions in which star formation occurs, and ultimately infer the role of the radio jets in triggering it.
Galaxy evolution and radiative properties in the early universe: Multi-wavelength analysis in cosmological simulations
Authors: Arata Shohei , Yajima Hidenobu , Nagamine Kentaro , Li Yuexing , Khochfar Sadegh
Published: June 2020

Recent observations have successfully detected UV or infrared flux from galaxies at the epoch of reionization. However, the origin of their radiative properties has not been fully understood yet. Combining cosmological hydrodynamic simulations and radiative transfer calculations, we present theoretical predictions of multi-wavelength radiative properties of the first galaxies at z = 6–15. We find that most of the gas and dust are ejected from star-forming regions due to supernova (SN) feedback, which allows UV photons to escape. We show that the peak of SED rapidly shifts between UV and infrared wavelengths on a timescale of 100 Myr due to intermittent star formation and feedback. When dusty gas covers the star-forming regions, the galaxies become bright in the observed-frame sub-millimeter wavelengths. In addition, we find that the escape fraction of ionizing photons also changes between 1–40% at z > 10. The mass fraction of H ii region changes with star formation history, resulting in fluctuations of metal lines and Lyman-α line luminosities. In the starbursting phase of galaxies with a halo mass ∼1011Mȯ (1012Mȯ), the simulated galaxy has L[OIII] ∼ 1042 (1043) erg s−1, which is consistent with the observed star-forming galaxies at z > 7. Our simulations suggest that deep [Cii] observation with ALMA can trace the distribution of neutral gas extending over ∼20 physical kpc. We also find that the luminosity ratio L[OIII]/L[CII] decreases with bolometric luminosity due to metal enrichment. Our simulations show that the combination of multi-wavelength observations by ALMA and JWST will be able to reveal the multi-phase ISM structure and the transition from starbursting to outflowing phases of high-z galaxies.
Serendipitous discovery of an “ALMA-only” galaxy at 5 < z < 6 in an ALMA 3-mm survey
Authors: Williams Christina C.
Published: June 2020

We discuss the serendipitous discovery of a dusty high-redshift galaxy in a small (8 arcmin2) ALMA 3-mm survey Williams et al. (2019). The galaxy was previously unknown and is absent from existing multi-wavelength catalogs (“ALMA-only”). Using the ALMA position as prior, we perform forced deblended photometry to constrain its spectral energy distribution. The spectral energy distribution is well described by a massive (M* = 1010.8 M⊙) and highly obscured (AV ∼ 4) galaxy at redshift z = 5.5 ± 1.1 with star formation rate ∼ 300 M⊙yr−1. Our small survey area implies an uncertain but large contribution to the cosmic star formation rate density, similar to the contribution from all ultraviolet-selected galaxies combined at this redshift. This galaxy likely traces an abundant population of massive galaxies absent from current samples of infrared-selected or sub-millimeter galaxies, but with larger space densities, higher duty cycles, and significant contribution to the cosmic star-formation rate and stellar mass densities.
The prevalence and physical properties of extremely low-luminosity galaxies in the early universe
Authors: Bouwens Rychard
Published: June 2020

Gravitational lensing from galaxy clusters has great potential for deriving the prevalence and physical properties of ultra-faint galaxies at early times, with recent very impressive results from the Hubble Frontier Fields program. Important issues in deriving the most accurate results are accurate constraints on source sizes and a robust treatment of uncertainties in the magnification models. Using > 3300 z = 2 – 10 galaxies behind the 6 Hubble Frontier Fields clusters and a forwards modeling approach, I describe the efforts of my collaborators and me to map out the galaxy luminosity functions at ∼ − 13 mag from z ∼ 9 to z ∼ 2, i.e, a factor of 1000 below Lå and to the typical luminosity of galaxies suspected to drive cosmic reionization. Additionally, I discuss the constraints we can obtain on the properties of faint sources, in particular their stellar masses, mass-to-light ratios, colors, and stellar population ages. I conclude with a prospective on using cluster lenses to study the distant universe with the James Webb Space Telescope.
Shedding light on high-redshift galaxies with the 21cm signal
Authors: Hutter Anne
Published: June 2020

Reionization represents an important epoch in the history in the Universe, when the first stars and galaxies gradually ionize the neutral hydrogen in the intergalactic medium (IGM). Understanding the nature of the ionizing sources, the associated ionization of the IGM, and its impact on subsequent structure formation and galaxy evolution by means of radiative feedback effects, represent key outstanding questions in current astrophysics. High-redshift galaxy observations and simulations have significantly extended our knowledge on the nature of high-redshift galaxies. However, essential properties such as the escape fraction of ionizing photons from galaxies into the IGM and their dependency on galactic properties remain essentially unknown, but determine significantly the distribution and time evolution of the ionized regions during reionization. Analyzing this ionization topology by means of the neutral hydrogen sensitive 21cm signal with radio interferometers such as SKA offers a complementary and unique opportunity to determine the nature of these first galaxies. I will show results from a self-consistent semi-numerical model of galaxy evolution and reionization, and discuss the potential of inferring galactic properties with the 21cm signal as well as the impact of reionization on the high-redshift galaxy population and its evolution.
Sub-galactic views of cold gas and dust in distant star-forming galaxies: Pushing the ∼ 100 pc frontier at z ∼ 3
Authors: Rujopakarn Wiphu
Published: June 2020

While the evolution of spatially-integrated properties of galaxies are relatively well constrained across cosmic time, many of the most fundamental processes are not well understood, especially down to the sub-galactic scales, where frontier questions in galaxy evolution lie: How did galactic spheroids form? How did galaxies and their supermassive black holes co-evolve? With the angular resolution capability of ∼tens of milliarcseconds, ALMA has conferred extinction- independent views of cold gas and dust distributions within individual z ∼ 1 – 4 galaxies at resolutions approaching ∼ 100 pc, thereby opening new avenues to study sub-galactic properties of galaxies at the peak of their assembly. In this talk, I will review recent findings and ongoing challenges enabled by ALMA's extinction-independent, spatially-resolved views of star forming galaxies, particularly the galactic substructures, e.g., clumps (or the lack thereof) from both field and gravitationally-lensed galaxies, and their implications on the bulge assembly scenario. I will also discuss a new synergistic approach between radio and millimeter observations (using, e.g., VLA and ALMA) to independently pinpoint the locations of star-forming region and AGN down to < 100 pc at z ∼ 3. Lastly, I will discuss the planned surveys with JWST in the first year of operation, and ways that the first datasets can be combined with ALMA to provide new breakthroughs and plan future observations to utilize Webb to the fullest.
Lessons from the local Universe
Authors: Weisz Daniel
Published: June 2020

Resolved galaxies in the local Universe are fundamentally connected to galaxies observed at all cosmic epochs. The IMF, extinction law, distance ladder, and stellar evolution are all anchored in observations of resolved stars in the nearby Universe. In this talk, I highlight new links between resolved galaxies and those in the higher redshift Universe, and discuss how future observations of resolved stars are essential for a complete and accurate census of galaxy evolution across cosmic time.
Identifiability in age/period/cohort mortality models
Authors: Hunt Andrew , Blake David
Published: June 2020

The addition of a set of cohort parameters to a mortality model can generate complex identifiability issues due to the collinearity between the dimensions of age, period and cohort. These issues can lead to robustness problems and difficulties making projections of future mortality rates. Since many modern mortality models incorporate cohort parameters, we believe that a comprehensive analysis of the identifiability issues in age/period/cohort mortality models is needed. In this paper, we discuss the origin of identifiability issues in general models before applying these insights to simple but commonly used mortality models. We then discuss how to project mortality models so that our forecasts of the future are independent of any arbitrary choices we make when fitting a model to data in order to identify the historical parameters.
Fertilizer placement effects on eclipta (Eclipta prostrata) growth and competition with container-grown ornamentals
Authors: Khamare Yuvraj , Marble S. Christopher , Chandler Annette
Published: June 2020

The objective of this study was to determine the effect of fertilizer placement on the growth of eclipta [Eclipta prostrata (L.) L.] and evaluate its interference with container-grown ornamental plants, including Japanese boxwood (Buxus microphylla Siebold & Zucc.) and ligustrum (Ligustrum lucidum W.T. Aiton). Results indicated that subdressing reduced E. prostrata shoot weight by 28%, 42%, and 46% at depths of 2.5, 5.0, and 7.5 cm, respectively, in comparison with a topdressed fertilizer treatment (a standard industry practice). Presence of E. prostrata reduced the growth of both ornamental species. Ligustrum shoot weight decreased as subdressing depth increased, while boxwood growth was most notably reduced at the 7.5-cm depth in comparison with topdressed containers. Overall, results indicated that subdressing may be an effective weed management strategy, but subdressing depth needs to be based on initial liner size to prevent possibly delays in production time.
Understanding the Interfacial Behavior of Typical Perfluorocarboxylic Acids at Surfactant‐Coated Aqueous Interfaces
Authors: Cheng Shumin , Du Lin , George Christian
Published: June 2020

Sea surface microlayers (SMLs) play an important role in the transport and fate of surfactants from both anthropogenic and biogenic sources. The formation of sea spray aerosols (SSAs) at the SML has been recognized as a critical pathway for the entry of surfactants into the atmosphere. Perfluorocarboxylic acids (PFCAs) have become increasingly concerning as a class of emerging organic pollutants, having high enrichment in surface seawaters due to their remarkable surface activity. Using artificial seawater coated by extensively existed surfactants, including stearyl alcohol (C18OH) and stearic acid (SA) as simplified models of the SML and fresh SSAs, the interfacial behaviors of soluble and insoluble PFCAs were examined. Information about lateral packing and chain conformation of films was obtained by means of Langmuir trough and infrared reflection‐absorption spectroscopy (IRRAS). Perfluorooctanoic acid (PFOA) dissolved in aqueous subphases was found to be incorporated into lipid monolayers via alterations in surface pressure‐area (π‐A) isotherms. With negligible solubility, perfluorotetradecanoic acid (PFTA) formed condensed mixed monolayers with other lipids at the air‐water interface. The mixed monolayers of C18OH/PFTA and SA/PFTA were expanded by the addition of sea salts into the pure water subphase. Compared with the π‐A isotherms of SA/PFTA, decreased molecular areas were observed for those of C18OH/PFTA. This research suggests that PFCAs can be incorporated into air‐water interfaces by acting as film‐forming materials. The introduction of PFCAs will alter the surface properties and thus the atmospheric fate and behavior of SSAs and SMLs.
Coupled Andean Growth and Foreland Basin Evolution, Campanian–Cenozoic Bagua Basin, Northern Peru
Authors: Moreno Federico , Garzione Carmala N. , George Sarah W. M. , Horton Brian K. , Williams Lauren , Jackson Lily J. , Carlotto Victor , Richter Fabiana , Bandeian Alice
Published: June 2020

Cenozoic sedimentary rocks of the intermontane Bagua Basin record the Andean orogenic history of northern Peru at ~4–7°S. The northern Peruvian Andes define the northern termination of the Central Andes and are comprised of a narrow, low‐elevation orogen relative to the rest of the Central Andes. New stratigraphic and sedimentologic field observations, subsidence analysis, and detrital zircon provenance analysis enable reconstruction of the regional tectonic history. Late Cretaceous to Paleocene detrital zircon U‐Pb age spectra from the Fundo El Triunfo and Rentema formations reveal active volcanism in the Western Cordillera as early as ~80 Ma and early exhumation of Mesozoic rocks in a nascent Marañon Fold‐Thrust Belt. Eocene fluvial deposits of the Cajaruro Formation record a progressive increase in shortening and volcanism in the Western Cordillera. The upper Eocene–middle Miocene fluvial succession of the Sambimera Formation records deposition in a proximal foredeep setting. Sambimera deposits contain syndepositional detrital zircon U‐Pb age populations that reveal a major Cenozoic magmatic source in the west. An erosive boundary separates the Sambimera from the overlying San Antonio Formation. The San Antonio Formation was deposited in an intermontane basin associated with uplift of the Eastern Cordillera at these latitudes. These results highlight a foreland progression of fold‐thrust deformation, with shortening concentrated in the Western Cordillera from latest Cretaceous to middle Miocene time. We suggest that the late Miocene transition to intermontane deposition in the Bagua Basin marks initial exhumation during shortening of the Eastern Cordillera in northern Peru.
Fieldwork in the Experimental Lakes Area Adapts to COVID-19
Authors: Evans Ogden Lesley
Published: June 2020

Though anticipating long days and hard work as a few key crew members do the job of many, researchers heading to the lakes this summer are excited to leave the house.
Global Heat Uptake by Inland Waters
Authors: Vanderkelen I. , van Lipzig N. P. M. , Lawrence D. M. , Droppers B. , Golub M. , Gosling S. N. , Janssen A. B. G. , Marcé R. , Schmied H. Müller , Perroud M. , Pierson D. , Pokhrel Y. , Satoh Y. , Schewe J. , Seneviratne S. I. , Stepanenko V. M. , Tan Z. , Woolway R. I. , Thiery W.
Published: June 2020

Heat uptake is a key variable for understanding the Earth system response to greenhouse gas forcing. Despite the importance of this heat budget, heat uptake by inland waters has so far not been quantified. Here we use a unique combination of global‐scale lake models, global hydrological models and Earth system models to quantify global heat uptake by natural lakes, reservoirs, and rivers. The total net heat uptake by inland waters amounts to 2.6 ± 3.2 ×1020 J over the period 1900–2020, corresponding to 3.6% of the energy stored on land. The overall uptake is dominated by natural lakes (111.7%), followed by reservoir warming (2.3%). Rivers contribute negatively (‐14%) due to a decreasing water volume. The thermal energy of water stored in artificial reservoirs exceeds inland water heat uptake by a factor ∼10.4. This first quantification underlines that the heat uptake by inland waters is relatively small, but non‐negligible.
Health-Related Decision-Making in Early Adolescents With Poorly Controlled Asthma
Authors: Turner Elise M. , Koskela-Staples Natalie , Voorhees Sara , McQuaid Elizabeth L. , Fedele David A.
Published: June 2020

Objective: Caregiver–adolescent collaborative decision-making is a key component of effective self-management, although there is limited understanding of this relationship in pediatric asthma. The current study examined the association between parent and youth decision-making and asthma self-management behaviors. Method: Participants included 33 youth ages 12–15 years ( M age = 13.18, SD = 1.16) with poorly controlled, persistent asthma and their caregivers. Participants completed the Family Asthma Management System Scale interview to assess core aspects of asthma management. The Decision Making Involvement Scale was administered to evaluate caregiver and adolescent behaviors during asthma-related decision-making. Results: Seventy percent of dyads reported discussing the adolescent’s asthma in the past 2 weeks. Forty-seven percent of families reached a final decision during the discussion, and 18% made a partial decision. Either the caregiver (41%) or the dyad together (27%) made the final decision. Youth whose parents made the final decision reported poorer responses to acute asthma symptoms ( p = .03, d = 0.99). Higher parental expression of information was associated with better family response to acute asthma symptoms, p = .045, R 2 = 0.69. Conclusions: Findings indicate that joint caregiver–youth collaborative decision-making and parent involvement in asthma-care decision-making were associated with better response to asthma exacerbations. A significant portion of families is not discussing their adolescent’s asthma, and future research is needed to identify what families are at risk for reduced communication regarding asthma-care decision-making. Health professionals should assess both caregiver and adolescent decision-making involvement when addressing asthma self-management.

Implications for Impact Statement

This study advances the idea that caregiver and youth collaboration during health-related decision-making is important for fostering disease management within pediatric asthma. Findings also highlight the need for disease management interventions targeting increased caregiver–youth communication surrounding the adolescent’s asthma care.
Reconsolidation-based treatment for fear of public speaking: a systematic pilot study using propranolol
Authors: Elsey James W. B. , Filmer Anna I. , Galvin Harriet R. , Kurath Jennifer D. , Vossoughi Linos , Thomander Linnea S. , Zavodnik Melissa , Kindt Merel
Published: June 2020

Pharmacological manipulation of memory reconsolidation opens up promising new avenues for anxiety disorder treatment. However, few studies have directly investigated reconsolidation-based approaches in subclinical or clinical populations, leaving optimal means of fear memory reactivation unknown. We conducted a systematic pilot study to assess whether a reconsolidation-based treatment could tackle public speaking anxiety in a subclinical sample (N = 60). As lab studies indicate that the duration of reactivation may be important for inducing reconsolidation, we investigated several speech lengths to help inform further translational efforts. Participants underwent a stress-inducing speech task composed of 3-min preparation, and from 0 to 9 min of public speaking, in 1-min increments. They then received either 40 mg of propranolol (n = 40) or placebo (n = 20), double-blind, allocated 4:2 for each speech duration. Participants performed a second speech 1 week post treatment, and were followed up with questionnaires 1- and 3 months later. Both self-reported speech distress and questionnaire measures of public speaking anxiety showed clear reductions following treatment. However, propranolol did not reliably outperform placebo, regardless of speech duration at treatment. Physiological responses (heart rate and salivary cortisol) to the public speaking task remained stable from treatment to test. These findings highlight the challenges facing the translation of laboratory research on memory reconsolidation into clinical interventions. Lack of explicit controls for factors beyond duration, such as ‘prediction error’, could explain these null findings, but positive results in clinical interventions are needed to demonstrate that taking such factors into account can deliver the promises of reconsolidation-based therapy.
TonEBP in dendritic cells mediates pro-inflammatory maturation and Th1/Th17 responses
Authors: Ye Byeong Jin , Lee Hwan Hee , Yoo Eun Jin , Lee Chae Young , Lee Jun Ho , Kang Hyun Je , Jeong Gyu Won , Park Hyun , Lee-Kwon Whaseon , Choi Soo Youn , Kwon Hyug Moo
Published: June 2020

Dendritic cells (DCs) are potent antigen-presenting cells that link the innate and adaptive immune responses; as such they play pivotal roles in initiation and progression of rheumatoid arthritis (RA). Here, we report that the tonicity-responsive enhancer-binding protein (TonEBP or NFAT5), a Rel family protein involved in the pathogenesis of autoimmune disease and inflammation, is required for maturation and function of DCs. Myeloid cell-specific TonEBP deletion reduces disease severity in a murine model of collagen-induced arthritis; it also inhibits maturation of DCs and differentiation of pathogenic Th1 and Th17 cells in vivo. Upon stimulation by TLR4, TonEBP promotes surface expression of major histocompatibility complex class II and co-stimulatory molecules via p38 mitogen-activated protein kinase. This is followed by DC-mediated differentiation of pro-inflammatory Th1 and Th17 cells. Taken together, these findings provide mechanistic basis for the pathogenic role of TonEBP in RA and possibly other autoimmune diseases.
Preparation of a germole-containing π-conjugated polymer by the Te–Li exchange reaction of a tellurophene-containing polymer
Authors: Zheng Feng , Tan Sia-Er , Yanamoto Yuki , Shida Naoki , Nishiyama Hiroki , Inagi Shinsuke , Tomita Ikuyoshi
Published: June 2020

The synthesis and optoelectronic functions of a germole-containing π-conjugated polymer prepared by the reaction of a lithiated polymer precursor are described. A regioregular organometallic polymer having 1,4-dilithio-1,3-butadiene and 9,9-dioctylfluorene-2,7-diyl units was generated by the reaction of a tellurophene-containing polymer having a number-average molecular weight (Mn) and molecular weight distribution (Mw/Mn) of 5900 and 1.9, respectively, with n-butyllithium (2.4 equiv) at −78 to −60 °C for 3 h. The prepared lithiated polymer was reacted with dimethylgermanium dichloride (1.5 equiv) at −60 °C to ambient temperature for 12 h in tetrahydrofuran to produce a π-conjugated polymer possessing 1,1-dimethylgermole-2,5-diyl units in 76% yield (Mn = 4400 and Mw/Mn = 1.7). The absorption maximum and onset of the obtained polymer were observed at 465 and 535 nm, respectively, in the UV-vis spectrum, from which the optical band gap of the polymer was estimated to be 2.31 eV. In the photoluminescence spectrum, the obtained polymer exhibits green fluorescence with an emission maximum of 547 nm and a quantum yield of 0.04. The chemical interaction of the dimethylgermole-containing π-conjugated polymer with fluoride was also examined in terms of the changes observed in the UV-vis absorption spectra.
An essential role for Argonaute 2 in EGFR-KRAS signaling in pancreatic cancer development
Authors: Shankar Sunita , Tien Jean Ching-Yi , Siebenaler Ronald F. , Chugh Seema , Dommeti Vijaya L. , Zelenka-Wang Sylvia , Wang Xiao-Ming , Apel Ingrid J. , Waninger Jessica , Eyunni Sanjana , Xu Alice , Mody Malay , Goodrum Andrew , Zhang Yuping , Tesmer John J. , Mannan Rahul , Cao Xuhong , Vats Pankaj , Pitchiaya Sethuramasundaram , Ellison Stephanie J. , Shi Jiaqi , Kumar-Sinha Chandan , Crawford Howard C. , Chinnaiyan Arul M.
Published: June 2020

Both KRAS and EGFR are essential mediators of pancreatic cancer development and interact with Argonaute 2 (AGO2) to perturb its function. Here, in a mouse model of mutant KRAS-driven pancreatic cancer, loss of AGO2 allows precursor lesion (PanIN) formation yet prevents progression to pancreatic ductal adenocarcinoma (PDAC). Precursor lesions with AGO2 ablation undergo oncogene-induced senescence with altered microRNA expression and EGFR/RAS signaling, bypassed by loss of p53. In mouse and human pancreatic tissues, PDAC progression is associated with increased plasma membrane localization of RAS/AGO2. Furthermore, phosphorylation of AGO2Y393 disrupts both the wild-type and oncogenic KRAS-AGO2 interaction, albeit under different conditions. ARS-1620 (G12C-specific inhibitor) disrupts the KRASG12C-AGO2 interaction, suggesting that the interaction is targetable. Altogether, our study supports a biphasic model of pancreatic cancer development: an AGO2-independent early phase of PanIN formation reliant on EGFR-RAS signaling, and an AGO2-dependent phase wherein the mutant KRAS-AGO2 interaction is critical for PDAC progression.
Extent of N-terminus exposure of monomeric alpha-synuclein determines its aggregation propensity
Authors: Stephens Amberley D. , Zacharopoulou Maria , Moons Rani , Fusco Giuliana , Seetaloo Neeleema , Chiki Anass , Woodhams Philippa J. , Mela Ioanna , Lashuel Hilal A. , Phillips Jonathan J. , De Simone Alfonso , Sobott Frank , Schierle Gabriele S. Kaminski
Published: June 2020

As an intrinsically disordered protein, monomeric alpha-synuclein (aSyn) occupies a large conformational space. Certain conformations lead to aggregation prone and non-aggregation prone intermediates, but identifying these within the dynamic ensemble of monomeric conformations is difficult. Herein, we used the biologically relevant calcium ion to investigate the conformation of monomeric aSyn in relation to its aggregation propensity. We observe that the more exposed the N-terminus and the beginning of the NAC region of aSyn are, the more aggregation prone monomeric aSyn conformations become. Solvent exposure of the N-terminus of aSyn occurs upon release of C-terminus interactions when calcium binds, but the level of exposure and aSyn’s aggregation propensity is sequence and post translational modification dependent. Identifying aggregation prone conformations of monomeric aSyn and the environmental conditions they form under will allow us to design new therapeutics targeted to the monomeric protein.
Human aminolevulinate synthase structure reveals a eukaryotic-specific autoinhibitory loop regulating substrate binding and product release
Authors: Bailey Henry J. , Bezerra Gustavo A. , Marcero Jason R. , Padhi Siladitya , Foster William R. , Rembeza Elzbieta , Roy Arijit , Bishop David F. , Desnick Robert J. , Bulusu Gopalakrishnan , Dailey Harry A. , Yue Wyatt W.
Published: June 2020

5′-aminolevulinate synthase (ALAS) catalyzes the first step in heme biosynthesis, generating 5′-aminolevulinate from glycine and succinyl-CoA. Inherited frameshift indel mutations of human erythroid-specific isozyme ALAS2, within a C-terminal (Ct) extension of its catalytic core that is only present in higher eukaryotes, lead to gain-of-function X-linked protoporphyria (XLP). Here, we report the human ALAS2 crystal structure, revealing that its Ct-extension folds onto the catalytic core, sits atop the active site, and precludes binding of substrate succinyl-CoA. The Ct-extension is therefore an autoinhibitory element that must re-orient during catalysis, as supported by molecular dynamics simulations. Our data explain how Ct deletions in XLP alleviate autoinhibition and increase enzyme activity. Crystallography-based fragment screening reveals a binding hotspot around the Ct-extension, where fragments interfere with the Ct conformational dynamics and inhibit ALAS2 activity. These fragments represent a starting point to develop ALAS2 inhibitors as substrate reduction therapy for porphyria disorders that accumulate toxic heme intermediates.
Author Correction: LRIG1 is a pleiotropic androgen receptor-regulated feedback tumor suppressor in prostate cancer
Authors: Li Qiuhui , Liu Bigang , Chao Hsueh-Ping , Ji Yibing , Lu Yue , Mehmood Rashid , Jeter Collene , Chen Taiping , Moore John R. , Li Wenqian , Liu Can , Rycaj Kiera , Tracz Amanda , Kirk Jason , Calhoun-Davis Tammy , Xiong Jie , Deng Qu , Huang Jiaoti , Foster Barbara A. , Gokhale Abhiram , Chen Xin , Tang Dean G.
Published: June 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Nonvolatile ferroelectric field-effect transistors
Authors: Chai Xiaojie , Jiang Jun , Zhang Qinghua , Hou Xu , Meng Fanqi , Wang Jie , Gu Lin , Zhang David Wei , Jiang An Quan
Published: June 2020

Future data-intensive applications will have integrated circuit architectures combining energy-efficient transistors, high-density data storage and electro-optic sensing arrays in a single chip to perform in situ processing of captured data. The costly dense wire connections in 3D integrated circuits and in conventional packaging and chip-stacking solutions could affect data communication bandwidths, data storage densities, and optical transmission efficiency. Here we investigated all-ferroelectric nonvolatile LiNbO3 transistors to function through redirection of conducting domain walls between the drain, gate and source electrodes. The transistor operates as a single-pole, double-throw digital switch with complementary on/off source and gate currents controlled using either the gate or source voltages. The conceived device exhibits high wall current density and abrupt off-and-on state switching without subthreshold swing, enabling nonvolatile memory-and-sensor-in-logic and logic-in-memory-and-sensor capabilities with superior energy efficiency, ultrafast operation/communication speeds, and high logic/storage densities.
Precise capture and dynamic relocation of nanoparticulate biomolecules through dielectrophoretic enhancement by vertical nanogap architectures
Authors: Yu Eui-Sang , Lee Hyojin , Lee Sun-Mi , Kim Jiwon , Kim Taehyun , Lee Jongsu , Kim Chulki , Seo Minah , Kim Jae Hun , Byun Young Tae , Park Seung-Chul , Lee Seung-Yeol , Lee Sin-Doo , Ryu Yong-Sang
Published: June 2020

Toward the development of surface-sensitive analytical techniques for biosensors and diagnostic biochip assays, a local integration of low-concentration target materials into the sensing region of interest is essential to improve the sensitivity and reliability of the devices. As a result, the dynamic process of sorting and accurate positioning the nanoparticulate biomolecules within pre-defined micro/nanostructures is critical, however, it remains a huge hurdle for the realization of practical surface-sensitive biosensors and biochips. A scalable, massive, and non-destructive trapping methodology based on dielectrophoretic forces is highly demanded for assembling nanoparticles and biosensing tools. Herein, we propose a vertical nanogap architecture with an electrode-insulator-electrode stack structure, facilitating the generation of strong dielectrophoretic forces at low voltages, to precisely capture and spatiotemporally manipulate nanoparticles and molecular assemblies, including lipid vesicles and amyloid-beta protofibrils/oligomers. Our vertical nanogap platform, allowing low-voltage nanoparticle captures on optical metasurface designs, provides new opportunities for constructing advanced surface-sensitive optoelectronic sensors.
Structural and functional evidence of bacterial antiphage protection by Thoeris defense system via NAD+ degradation
Authors: Ka Donghyun , Oh Hyejin , Park Eunyoung , Kim Jeong-Han , Bae Euiyoung
Published: June 2020

The intense arms race between bacteria and phages has led to the development of diverse antiphage defense systems in bacteria. Unlike well-known restriction-modification and CRISPR-Cas systems, recently discovered systems are poorly characterized. One such system is the Thoeris defense system, which consists of two genes, thsA and thsB. Here, we report structural and functional analyses of ThsA and ThsB. ThsA exhibits robust NAD+ cleavage activity and a two-domain architecture containing sirtuin-like and SLOG-like domains. Mutation analysis suggests that NAD+ cleavage is linked to the antiphage function of Thoeris. ThsB exhibits a structural resemblance to TIR domain proteins such as nucleotide hydrolases and Toll-like receptors, but no enzymatic activity is detected in our in vitro assays. These results further our understanding of the molecular mechanism underlying the Thoeris defense system, highlighting a unique strategy for bacterial antiphage resistance via NAD+ degradation.
Specific Electrogram Characteristics Identify the Extra-Pulmonary Vein Arrhythmogenic Sources of Persistent Atrial Fibrillation – Characterization of the Arrhythmogenic Electrogram Patterns During Atrial Fibrillation and Sinus Rhythm
Authors: Jadidi Amir , Nothstein Mark , Chen Juan , Lehrmann Heiko , Dössel Olaf , Allgeier Jürgen , Trenk Dietmar , Neumann Franz-Josef , Loewe Axel , Müller-Edenborn Björn , Arentz Thomas
Published: June 2020

Identification of atrial sites that perpetuate atrial fibrillation (AF), and ablation thereof terminates AF, is challenging. We hypothesized that specific electrogram (EGM) characteristics identify AF-termination sites (AFTS). Twenty-one patients in whom low-voltage-guided ablation after pulmonary vein isolation terminated clinical persistent AF were included. Patients were included if short RF-delivery for <8sec at a given atrial site was associated with acute termination of clinical persistent AF. EGM-characteristics at 21 AFTS, 105 targeted sites without termination and 105 non-targeted control sites were analyzed. Alteration of EGM-characteristics by local fibrosis was evaluated in a three-dimensional high resolution (100 µm)-computational AF model. AFTS demonstrated lower EGM-voltage, higher EGM-cycle-length-coverage, shorter AF-cycle-length and higher pattern consistency than control sites (0.49 ± 0.39 mV vs. 0.83 ± 0.76 mV, p < 0.0001; 79 ± 16% vs. 59 ± 22%, p = 0.0022; 173 ± 49 ms vs. 198 ± 34 ms, p = 0.047; 80% vs. 30%, p < 0.01). Among targeted sites, AFTS had higher EGM-cycle-length coverage, shorter local AF-cycle-length and higher pattern consistency than targeted sites without AF-termination (79 ± 16% vs. 63 ± 23%, p = 0.02; 173 ± 49 ms vs. 210 ± 44 ms, p = 0.002; 80% vs. 40%, p = 0.01). Low voltage (0.52 ± 0.3 mV) fractionated EGMs (79 ± 24 ms) with delayed components in sinus rhythm (‘atrial late potentials’, respectively ‘ALP’) were observed at 71% of AFTS. EGMs recorded from fibrotic areas in computational models demonstrated comparable EGM-characteristics both in simulated AF and sinus rhythm. AFTS may therefore be identified by locally consistent, fractionated low-voltage EGMs with high cycle-length-coverage and rapid activity in AF, with low-voltage, fractionated EGMs with delayed components/ ‘atrial late potentials’ (ALP) persisting in sinus rhythm.
Statistical analysis of longitudinal data on tumour growth in mice experiments
Authors: Zavrakidis Ioannis , Jóźwiak Katarzyna , Hauptmann Michael
Published: June 2020

We consider mice experiments where tumour cells are injected so that a tumour starts to grow. When the tumour reaches a certain volume, mice are randomized into treatment groups. Tumour volume is measured repeatedly until the mouse dies or is sacrificed. Tumour growth rates are compared between groups. We propose and evaluate linear regression for analysis accounting for the correlation among repeated measurements per mouse. More specifically, we examined five models with three different variance-covariance structures in order to recommend the least complex method for small to moderate sample sizes encountered in animal experiments. We performed a simulation study based on data from three previous experiments to investigate the properties of estimates of the difference between treatment groups. Models were estimated via marginal modelling using generalized least squares and restricted maximum likelihood estimation. A model with an autoregressive (AR-1) covariance structure was efficient and unbiased retaining nominal coverage and type I error when the AR-1 variance-covariance matrix correctly specified the association between repeated measurements. When the variance-covariance was misspecified, that model was still unbiased but the type I error and the coverage rates were affected depending on the degree of misspecification. A linear regression model with an autoregressive (AR-1) covariance structure is an adequate model to analyse experiments that compare tumour growth rates between treatment groups.
Vasopressin receptor 2 mutations in the nephrogenic syndrome of inappropriate antidiuresis show different mechanisms of constitutive activation for G protein coupled receptors
Authors: Vezzi Vanessa , Ambrosio Caterina , Grò Maria Cristina , Molinari Paola , Süral Gökçe , Costa Tommaso , Onaran H. Ongun , Cotecchia Susanna
Published: June 2020

Vasopressin receptor 2 (V2R) mutations causing the nephrogenic syndrome of inappropriate antidiuresis (NSIAD) can generate two constitutively active receptor phenotypes. One type results from residue substitutions in several V2R domains and is sensitive to vaptan inverse agonists. The other is only caused by Arg 137 replacements and is vaptan resistant. We compared constitutive and agonist-driven interactions of the vaptan-sensitive F229V and vaptan-resistant R137C/L V2R mutations with β-arrestin 1, β-arrestin 2, and Gαs, using null fibroblasts reconstituted with individual versions of the ablated transduction protein genes. F229V displayed very high level of constitutive activation for Gs but not for β-arrestins, and enhanced or normal responsiveness to agonists and inverse agonists. In contrast, R137C/L mutants exhibited maximal levels of constitutive activation for βarrestin 2 and Gs, minimal levels for β-arrestin 1, but a sharp decline of ligands sensitivity at all transducer interactions. The enhanced constitutive activity and reduced ligand sensitivity of R137 mutants on cAMP signaling persisted in cells lacking β-arrestins, indicating that these are intrinsic molecular properties of the mutations, not the consequence of altered receptor trafficking. The results suggest that the two groups of NSIAD mutations represent two distinct molecular mechanisms of constitutive activation in GPCRs.
Amyloid Aggregation of Insulin: An Interaction Study of Green Tea Constituents
Authors: Gancar Miroslav , Kurin Elena , Bednarikova Zuzana , Marek Jozef , Mucaji Pavel , Nagy Milan , Gazova Zuzana
Published: June 2020

Exogenous insulin, used as a therapeutic agent for diabetes, forms insoluble deposits containing amyloid fibrillar structures near the administration site. We have analyzed the in vitro anti-amyloid activity of four green tea constituents: (-)-epigallocatechin gallate (EGCG), (-)-epicatechin (EC), gallic acid (GA), caffeine (CF), and their equimolar mixtures. Regarding individually tested compounds, only EGCG inhibited the fibrillization process. The individual EC, GA, and CF molecules were ineffective. The presence of EGCG in equimolar combinations with GA, EC, or CF was required for the inhibitory activity of most mixtures. Molecular docking revealed that EGCG interacts with an essential amyloidogenic region of insulin chain B. Individually inactive GA had a potentiating effect on the activity of EGCG. In contrast, EC and CF had a negative impact on the activity of the mixtures. We have observed diverse morphology and the amount of insulin amyloid aggregates formed in the presence of studied compounds. The distinct types of amyloid aggregates created in vitro in the presence of EGCG and other green tea constituents were characterized. Results indicate that the biological activity of individual molecules is not directly applicable to the pooled samples effects prediction.