bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ethanol modulates the effector functions of human monocyte-derived macrophages in response toParacoccidioides brasiliensisyeast cells
Authors: de Castro Lívia Furquim , de Araújo Mathias Kamila , Nunes Júlia Vieira , Galastri Ana Lúcia Bergamasco , da Silva Dennis Henrique Leandro , Longhi Larissa Nara Alegrini , de Souza Lima Blotta Maria Heloisa , Mamoni Ronei Luciano 
Published: January 2021

AbstractWe aimed to investigate the effects of ethanol and its metabolites (β-hydroxybutyrate and sodium acetate) in the effector functions of macrophages in response to Paracoccidioides brasiliensis yeast cells and to determine their influence in the development of the adaptive response. Purified peripheral blood monocytes were differentiated into macrophages and were treated with ethanol, β-hydroxybutyrate, and sodium acetate, and stimulated with P. brasiliensis yeast cells and evaluated for their phenotypic characteristics, functional activity, and capability to induce T cells activation/differentiation. We found that the ethanol treatment diminished the expression of HLA-AB, HLA-DR, CD80, and CD86, modulating the expression of dectin-1, as well as Syk phosphorylation. The ethanol treatment increased the phagocytic activity, expression of CD206, and IL-10 production; however, reduced ROS production, fungicidal activity, caspase-1 cleavage, and IL-1β and IL-6 production. Our data also showed that the presence of ethanol reduced the differentiation of Th1 and Th17 cells and increased the frequency of Th2 cells. Our results indicated that ethanol exposure could suppress effector function of macrophages, possibly leading to the polarization of M2 macrophages. The ethanol modulates the expression of costimulatory and antigen-presentation molecules and interferes with the NLRP3 inflammasome. Altogether, these alterations affect the development of the adaptive response, decreasing the frequency of IL-17, IL-22, and IFN- γ producing cells, and increasing the frequency of IL-4 producing cells. Therefore, exposure to ethanol can impair the capability of macrophages to exert their effector functions and activate the acquired response related to resistance to P. brasiliensis infection.
The bursty star formation history of the Fornax dwarf spheroidal galaxy revealed with the HST
Authors: Rusakov V , Monelli M , Gallart C , Fritz T K , Ruiz-Lara T , Bernard E J , Cassisi. S 
Published: January 2021

ABSTRACT
We present a new derivation of the star formation history (SFH) of the dSph galaxy Fornax in two central regions, characterized by unprecedented precision and age resolution. It reveals that star formation has proceeded in sharp bursts separated by periods of low level or quiescent activity. The SFH was derived through colour–magnitude diagram (CMD) fitting of two extremely deep Hubble Space Telescope CMDs, sampling the centre and one core radius. The attained age resolution allowed us to single out a major star formation episode at early times, a second strong burst 4.6 ± 0.4 Gyr ago and recent intermittent episodes ∼2–0.2 Gyr ago. Detailed testing with mock stellar populations was used to estimate the duration of the main bursts and study the occurrence of low-level star formation between them. The SFHs in both regions show common features, with activity at the same epochs and similar age–metallicity relationship. However, clear indications of a spatial gradient were also found, with mean age increasing with radius and star formation episodes being more prolonged in the centre. While some galaxy evolution models predict bursty SFHs in dwarf galaxies and thus a secular origin of the observed SFH cannot be excluded in Fornax, other evidence points to possible mergers or interactions as the cause of its bursty SFH. In particular, we calculated the Fornax orbit relative to the closest dwarfs and the Milky Way and observed a correspondence between the main intermediate-age and young events and peri-passages of Fornax around the Milky Way, possibly indicating tidally induced star formation.
Periods and classifications of RR Lyrae stars in the globular cluster M15
Authors: Hoffman Andrew M , Murakami Yukei S , Zheng WeiKang , Stahl Benjamin E , Filippenko Alexei V 
Published: January 2021

ABSTRACT
We present measurements of the periods, amplitudes, and types of 74 RR Lyrae stars in the globular cluster M15 derived from Nickel 1 m telescope observations conducted at Lick Observatory in 2019 and 2020. Of these RR Lyrae stars, two were previously reported but without a determination of the period. In addition, we identify five Type II Cepheid variable stars for which we report three novel period determinations, and a further 34 stars with uncertain classifications and periods. We discuss the development and subsequent application to our data of a new python package, Period-determination and Identification Pipeline Suite (pips), based on a new adaptive free-form fitting technique to detect the periods of variable stars with a clear treatment of uncertainties.
Statistical microlensing towards magnified high-redshift star clusters
Authors: Dai Liang 
Published: January 2021

ABSTRACT
We study light variability of gravitationally magnified high-redshift star clusters induced by a foreground population of microlenses. This arises as the incoherent superposition of light variations from many source stars traversing the random magnification pattern on the source plane. The light curve resembles a scale-invariant, Gaussian process on time-scales of years to decades, while exhibits rapid and frequent micro-caustic crossing flares of larger amplitudes on time-scales of days to months. For a concrete example, we study a young Lyman-continuum-leaking star cluster in the Sunburst Arc at z = 2.37. We show that one magnified image happens to be intervened by a foreground galaxy, and hence should exhibit a variable flux at the 1–$2{{\ \rm per\ cent}}$ level, which is measurable in space with ∼1–$3\,$ ks exposures on the Hubble Space Telescope and more easily with the James Webb Space Telescope, or even from the ground using a ∼4-m telescope without adaptive optics. Detailed measurement of this variability can help determine the absolute macro magnification and hence the intrinsic mass and length scales of the star cluster, test synthetic stellar population models, and probe multiplicity of massive stars. Furthermore, monitoring the other lensed images of the star cluster, which are free from significant intervention by foreground microlenses, can allow us to probe planetary to stellar mass compact objects constituting as little as a few per cent of the dark matter. Given the typical surface density of intracluster stars, we expect this phenomenon to be relevant for other extragalactic star clusters lensed by galaxy clusters.
Simulating dust grain-radiation coupling on a moving mesh
Authors: McKinnon Ryan , Kannan Rahul , Vogelsberger Mark , O’Neil Stephanie , Torrey Paul , Li Hui 
Published: January 2021

ABSTRACT
We present a model for the interaction between dust and radiation fields in the radiation hydrodynamic code arepo-rt, which solves the moment-based radiative transfer equations on an unstructured moving mesh. Dust is directly treated using live simulation particles, each of which represent a population of grains that are coupled to hydrodynamic motion through a drag force. We introduce methods to calculate radiation pressure on and photon absorption by dust grains. By including a direct treatment of dust, we are able to calculate dust opacities and update radiation fields self-consistently based on the local dust distribution. This hybrid scheme coupling dust particles to an unstructured mesh for radiation is validated using several test problems with known analytic solutions, including dust driven via spherically symmetric flux from a constant luminosity source and photon absorption from radiation incident on a thin layer of dust. Our methods are compatible with the multifrequency scheme in arepo-rt, which treats UV, optical photons as single scattered and IR photons as multi scattered. At IR wavelengths, we model heating of and thermal emission from dust. Dust and gas are not assumed to be in local thermodynamic equilibrium but transfer energy through collisional exchange. We estimate dust temperatures by balancing these dust-radiation and dust-gas energy exchange rates. This framework for coupling dust and radiation can be applied in future radiation hydrodynamic simulations of galaxy formation.
Solid-phase XRN1 reactions for RNA cleavage: application in single-molecule sequencing
Authors: Athapattu Uditha S , Amarasekara Charuni A , Immel Jacob R , Bloom Steven , Barany Francis , Nagel Aaron C , Soper Steven A 
Published: January 2021

Abstract
Modifications in RNA are numerous (∼170) and in higher numbers compared to DNA (∼5) making the ability to sequence an RNA molecule to identify these modifications highly tenuous using next generation sequencing (NGS). The ability to immobilize an exoribonuclease enzyme, such as XRN1, to a solid support while maintaining its activity and capability to cleave both the canonical and modified ribonucleotides from an intact RNA molecule can be a viable approach for single-molecule RNA sequencing. In this study, we report an enzymatic reactor consisting of covalently attached XRN1 to a solid support as the groundwork for a novel RNA exosequencing technique. The covalent attachment of XRN1 to a plastic solid support was achieved using EDC/NHS coupling chemistry. Studies showed that the solid-phase digestion efficiency of model RNAs was 87.6 ± 2.8%, while the XRN1 solution-phase digestion for the same model was 78.3 ± 4.4%. The ability of immobilized XRN1 to digest methylated RNA containing m6A and m5C ribonucleotides was also demonstrated. The processivity and clipping rate of immobilized XRN1 secured using single-molecule fluorescence measurements of a single RNA transcript demonstrated a clipping rate of 26 ± 5 nt s−1 and a processivity of &gt;10.5 kb at 25°C.
Propofol and sevoflurane affect intra-operative memory formation of words differently
Authors: Orena Eleonora F. , Landucci Francesco , Ayadi Roberta , Caldiroli Dario , Papagno Costanza 
Published: January 2021

BACKGROUND
Memory priming seems possible even during apparently adequate anaesthesia. However, the effects of different anaesthetics and type of stimuli, by virtue of their specific neural underpinnings, have not been considered.

OBJECTIVE
To determine if intra-operative implicit memory is affected by the type of anaesthesia (propofol or sevoflurane) or by the type of stimuli (abstract or concrete words).

DESIGN
Two consecutive, randomised controlled experiments.

SETTING
Neurological institute in Milan, Italy.

PATIENTS
Forty-three patients undergoing anaesthesia with propofol (experiment 1) and 32 patients undergoing anaesthesia with sevoflurane (experiment 2). Patients were ASA I or II, age 18 to 65 years, native Italian speakers, right-handed and without any condition affecting memory or hearing.

INTERVENTION
During anaesthesia, the patients heard a list of either concrete or abstract words or no words at all (controls). Explicit memory was tested with an explicit recall task and the Brice Interview; implicit memory was assessed through a word stem completion test.

OUTCOME MEASURES
The number of explicitly recalled words, positivity to the Brice Interview, the proportion of target and nontarget hits, and a derived implicit memory score.

RESULTS
With propofol, the proportion of target hits was significantly greater than the proportion of nontarget hits for the concrete word experimental group (P = 0.018). The implicit memory score of the concrete word experimental group was significantly higher than the score of both the abstract word experimental group (P
= 0.000) and the concrete word control group (P = 0.023). With sevoflurane, the proportion of target hits was significantly higher than the proportion of nontarget hits for the abstract word experimental group only (P = 0.027). No patients had a BIS above 60 and no one could recall intra-operative events or words.

CONCLUSION
Intra-operative memory for words can form during apparently adequate BIS-guided anaesthesia but is modified by propofol or sevoflurane acting on different brain targets. Further studies on larger samples and using neuroimaging techniques are needed.

TRIAL REGISTRATION
Clinicaltrials.gov identifier: NCT03727464.
Genetic depletion studies define receptor usage by virulent hantaviruses in human endothelial cells
Authors: Dieterle M. Eugenia , Solà-Riera Carles , Jangra Rohit K. , Ye Chunyan , Goodfellow Samuel M. , Mittler Eva , Kasikci Ezgi , Bradfute Steven B. , Klingström Jonas , Chandran Kartik 
Published: January 2021

AbstractHantaviruses are a large group of RNA viruses that include known epidemic threats and other agents poised for emergence. Several rodent-borne hantaviruses cause zoonoses accompanied by severe illness and death. However, assessments of zoonotic risk and the development of countermeasures alike are challenged by our limited knowledge of the molecular mechanisms of hantavirus infection, including the identities of cell entry receptors and their roles in influencing viral host range and virulence. Previous work has implicated several cell-surface molecules, most notably β3- and β1-containing integrin heterodimers, decay-accelerating factor (DAF), and the cadherin superfamily protein protocadherin-1 (PCDH1), in hantavirus entry in endothelial cells, the major targets of viral infection in humans. Despite the fact that β3/β1 integrins have been presumed to be the major hantavirus entry receptors for over two decades, rigorous genetic evidence supporting their requirement, and that of DAF as an entry cofactor, is lacking. Here, we used CRISPR/Cas9 engineering to knock out four candidate hantaviral receptors, singly and in combination, in a human endothelial cell line that recapitulates the properties of primary microvascular endothelial cells. PCDH1 loss substantially reduced entry and infection by a subset of hantaviruses endemic to the Americas. In contrast, the loss of β3 integrin, β1 integrin, and/or DAF had little or no effect on entry by any of a large panel of hantaviruses tested. We conclude that the major host molecules necessary for endothelial cell entry by PCDH1-independent hantaviruses remain to be discovered.
Comprehensive mapping of mutations to the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human serum antibodies
Authors: Greaney Allison J. , Loes Andrea N. , Crawford Katharine H.D. , Starr Tyler N. , Malone Keara D. , Chu Helen Y. , Bloom Jesse D. 
Published: January 2021

AbstractThe evolution of SARS-CoV-2 could impair recognition of the virus by human antibody-mediated immunity. To facilitate prospective surveillance for such evolution, we map how convalescent serum antibodies are impacted by all mutations to the spike’s receptor-binding domain (RBD), the main target of serum neutralizing activity. Binding by polyclonal serum antibodies is affected by mutations in three main epitopes in the RBD, but there is substantial variation in the impact of mutations both among individuals and within the same individual over time. Despite this inter- and intra-person heterogeneity, the mutations that most reduce antibody binding usually occur at just a few sites in the RBD’s receptor binding motif. The most important site is E484, where neutralization by some sera is reduced >10-fold by several mutations, including one in emerging viral lineages in South Africa and Brazil. Going forward, these serum escape maps can inform surveillance of SARS-CoV-2 evolution.
Glycan reactive anti-HIV-1 antibodies bind the SARS-CoV-2 spike protein but do not block viral entry
Authors: Mannar Dhiraj , Leopold Karoline , Subramaniam Sriram 
Published: January 2021

AbstractThe SARS-CoV-2 spike glycoprotein is a focal point for vaccine immunogen and therapeutic antibody design, and also serves as a critical antigen in the evaluation of immune responses to COVID-19. A common feature amongst enveloped viruses such as SARS-CoV-2 and HIV-1 is the propensity for displaying host-derived glycans on entry spike proteins. Similarly displayed glycosylation motifs can serve as the basis for glyco-epitope mediated cross-reactivity by antibodies, which can have important implications on virus neutralization, antibody-dependent enhancement (ADE) of infection, and the interpretation of antibody titers in serological assays. From a panel of nine anti-HIV-1 gp120 reactive antibodies, we selected two (PGT126 and PGT128) that displayed high levels of cross-reactivity with the SARS-CoV-2 spike. We report that these antibodies are incapable of neutralizing pseudoviruses expressing SARS-CoV-2 spike proteins and are unlikely to mediate ADE via FcγRII receptor engagement. Nevertheless, ELISA and other immunoreactivity experiments demonstrate these antibodies are capable of binding the SARS-CoV-2 spike in a glycan-dependent manner. These results contribute to the growing literature surrounding SARS-CoV-2 S cross-reactivity, as we demonstrate the ability for cross-reactive antibodies to interfere in immunoassays.
Dynamic closed states of a ligand-gated ion channel captured by cryo-EM and simulations
Authors: Rovšnik Urška , Zhuang Yuxuan , Forsberg Björn O , Carroni Marta , Yvonnesdotter Linnea , Howard Rebecca J , Lindahl Erik 
Published: January 2021

AbstractLigand-gated ion channels are critical mediators of electrochemical signal transduction across evolution. Biophysical and pharmacological characterization of these receptor proteins relies on high-quality structures in multiple, subtly distinct functional states. However, structural data in this family remain limited, particularly for resting and intermediate states on the activation pathway. Here we report cryo-electron microscopy (cryo-EM) structures of the proton-activatedGloeobacter violaceusligand-gated ion channel (GLIC) under three pH conditions. Decreased pH was associated with improved resolution and sidechain rearrangements at the subunit/domain interface, particularly involving functionally important residues in the β1-β2 and M2-M3 loops. Molecular dynamics simulations substantiated flexibility in the closed-channel extracellular domains relative to the transmembrane ones, and supported electrostatic remodeling around E35 and E243 in proton-induced gating. Exploration of secondary cryo-EM classes further indicated a low-pH population with an expanded pore. These results support a dissection of protonation and activation steps in pH-stimulated conformational cycling in GLIC, including interfacial rearrangements largely conserved in the pentameric channel family.
Phosphoproteomic Landscape of AML Cells Treated with the ATP-Competitive CK2 Inhibitor CX-4945
Authors: Rosales Mauro , Rodríguez-Ulloa Arielis , Besada Vladimir , Ramón Ailyn C. , Pérez George V. , Ramos Yassel , Guirola Osmany , González Luis J. , Zettl Katharina , Wiśniewski Jacek R. , Perera Yasser , Perea Silvio E. 
Published: January 2021

AbstractCasein kinase 2 (CK2) regulates a plethora of proteins with pivotal roles in solid and hematological neoplasia. Particularly, in acute myeloid leukemia (AML) CK2 has been pointed as an attractive therapeutic target and prognostic marker. Here, we explored the impact of CK2 inhibition over the phosphoproteome of two cell lines representing major AML subtypes. Quantitative phosphoproteomic analysis was conducted to evaluate changes in phosphorylation levels after incubation with the ATP-competitive CK2 inhibitor CX-4945. Functional enrichment, network analysis, and database mining were performed to identify biological processes, signaling pathways, and CK2 substrates that are responsive to CX-4945. A total of 273 and 1310 phosphopeptides were found differentially modulated in HL-60 and OCI-AML3 cells, respectively. Despite regulated phosphopeptides belong to proteins involved in multiple biological processes and signaling pathways, most of these perturbations can be explain by direct CK2 inhibition rather than off-target effects. Furthermore, CK2 substrates regulated by CX-4945 are mainly related to mRNA processing, translation, DNA repair, and cell cycle. Overall, we evidenced that CK2 inhibitor CX-4945 impinge on mediators of signaling pathways and biological processes essential for primary AML cells survival and chemosensitivity, reinforcing the rationale behind the pharmacologic blockade of protein kinase CK2 for AML targeted therapy.
Structural Characteristics and Proton Conductivity of the Gel Within the Electrosensory Organs of Cartilaginous Fishes
Authors: Phillips Molly , Wheeler Alauna , Robinson Matthew J. , Leppert Valerie , Jia Manping , Rolandi Marco , Hirst Linda S. , Amemiya Chris T. 
Published: January 2021

AbstractThe Ampullae of Lorenzini (AoL) of cartilaginous fishes are sensory organs used to detect environmental electric fields. The proximal ends of the organs are externally visible as pores in the skin that lead into gel-filled tubular canals which terminate in rounded chambers filled with highly specialized electrosensory cells. The viscoelastic gel that fills the organs is composed of proteins and polysaccharides that are not yet completely characterized but are thought to play a critical role in the electrosensing mechanism. Although recent studies have identified various components of AoL gel, it has remained unclear how the component molecules are structurally arranged and how their structure influences the overall function of the AoL. Here we present the first microscopic descriptions and x-ray scattering data from AoL gel extracted from spotted ratfish (Hydrolagus colliei). Our results suggest that AoL gel is colloidal in nature and composed of spherical globules that are approximately 10-100 nm in size. We investigated the structural influence of the protein components of the gel specifically by analyzing gel that had been digestedin situvia enzymatic proteolysis. By comparing gel before and after digestion using microscopy, x-ray scattering analyses, and proton conductivity measurements, we directly observed the structural and functional influence of proteins in AoL gel. The findings described here represent the first detailed structural analysis of AoL gel and lay the groundwork for more detailed studies into the specific interactions of molecules inside AoL gel at the nanoscale, with particular reference to their mechanistic role in electrosensing.
Optogenetic stimulation of VIPergic SCN neurons induces photoperiodic changes in the mammalian circadian clock
Authors: Tackenberg Michael C. , Hughey Jacob J. , McMahon Douglas G. 
Published: January 2021

SummaryCircadian clocks play key roles in how organisms respond to and even anticipate seasonal change in day length, or photoperiod. In mammals, photoperiod is encoded by the central circadian pacemaker in the brain, the suprachiasmatic nucleus (SCN). The subpopulation of SCN neurons that secrete the neuropeptide VIP mediate the transmission of light information within the SCN neural network, suggesting a role for these neurons in circadian plasticity in response to light information that has yet to be directly tested. Here, we usedin vivooptogenetic stimulation of VIPergic SCN neurons followed byex vivoPERIOD 2::LUCIFERASE (PER2::LUC) bioluminescent imaging to test whether activation of this SCN neuron sub-population can induce SCN network changes that are hallmarks of photoperiodic encoding. We found that optogenetic stimulation designed to mimic a long photoperiod indeed altered subsequent SCN entrained phase, increased the phase dispersal of PER2 rhythms within the SCN network, and shortened SCN free-running period – similar to the effects of a true extension of photoperiod. Optogenetic stimulation also induced analogous changes on related aspects of locomotor behaviorin vivo. Thus, selective activation of VIPergic SCN neurons induces photoperiodic network plasticity in the SCN which underpins photoperiodic entrainment of behavior.