bluuebunny/crossref_metadata_2025 huggingface dataset:
How migration intentions change during periods of political instability and violence: Panel survey evidence from Kenya
Authors: Ruhe Constantin
Published: September 2021

Forced migration research suggests that violence plays a central role in individuals’ decision to flee. However, research has not yet examined how individuals form migration decisions in violent contexts over time. I argue that forced migration decision making consists of anticipatory and reactive processes. Distinguishing these stages improves our understanding of seemingly contradictory evidence on the violence–displacement link. I posit that some individuals anticipate security risks based on personal characteristics such as affiliations with specific identity groups and based on previous experiences. Consequently, they consider leaving due to security concerns relatively early and are likely to flee in anticipation of violence. Others will only react to direct consequences of political conflict, but leave quickly when they experience violence regardless of previous intentions. To evaluate this argument empirically, I analyze an original panel dataset among the adult population of Nairobi and Mombasa which tracks individual migration considerations and actual displacement during the violent 2017 Kenyan elections over time. The longitudinal design disaggregates migration decision making and studies when and for which reasons people consider leaving as well as when individuals implement their plans to leave their homes. The results underscore the theoretical argument: Some individuals react quickly to changing events and start to consider leaving their homes. Moreover, these considerations translate into action: individuals who report security-related migration intentions are much more likely to flee. Regardless of the previous migration plans, however, a second group of individuals flees once they personally experience violence. The decision logic mirrors two-step models of non-conflict migration decision making.
Identity or interests? Religious conservatives’ attitudes toward Syrian refugees in Turkey
Authors: Morgül Kerem , Savaşkan Osman
Published: September 2021

The literature on religion and migration attitudes shows that religious concerns may play a significant role in motivating anti-migrant sentiments. Most of these studies, however, focus on Western countries, where religious beliefs and symbols have been utilized to amplify the cultural differences between natives and newcomers. In this article, we contribute to this scholarship by examining religious conservatives’ attitudes toward Syrian refugees in Turkey, a Muslim-majority country where political elites have employed religiously informed narratives to mitigate hostility toward migrants. To do so, we use a sequential mixed methods design, whereby nine focus group discussions conducted with religious conservatives in Istanbul in November 2019 were complemented by an original survey of Istanbul residents fielded in July–August 2020. Our results indicate that religious motives have a bias-reducing effect on conservative Sunni Muslims’ attitudes toward Syrian refugees; however, such motives are not powerful enough to overcome personal economic concerns. More broadly, the results suggest that researchers should be cautious about generalizing findings from Western societies to non-Western contexts and pay greater attention to the ways in which cultural and economic factors may interact in shaping natives’ migration preferences.
Calibration of bias and scatter involved in cluster mass measurements using optical weak gravitational lensing
Authors: Grandis Sebastian , Bocquet Sebastian , Mohr Joseph J , Klein Matthias , Dolag Klaus
Published: September 2021

Cosmological inference from cluster number counts is systematically limited by the accuracy of the mass calibration, i.e. the empirical determination of the mapping between cluster selection observables and halo mass. In this work we demonstrate a method to quantitatively determine the bias and uncertainties in weak-lensing (WL) mass calibration. To this end, we extract a library of projected matter density profiles from hydrodynamical simulations. Accounting for shear bias and noise, photometric redshift uncertainties, mis-centreing, cluster member contamination, cluster morphological diversity, and line-of-sight projections, we produce a library of shear profiles. Fitting a one-parameter model to these profiles, we extract the so-called WL mass MWL. Relating the WL mass to the halo mass from gravity-only simulations with the same initial conditions as the hydrodynamical simulations allows us to estimate the impact of hydrodynamical effects on cluster number counts experiments. Creating new shear libraries for ∼1000 different realizations of the systematics provides a distribution of the parameters of the WL to halo mass relation, reflecting their systematic uncertainty. This result can be used as a prior for cosmological inference. We also discuss the impact of the inner fitting radius on the accuracy, and determine the outer fitting radius necessary to exclude the signal from neighbouring structures. Our method is currently being applied to different Stage III lensing surveys, and can easily be extended to Stage IV lensing surveys.
Variable stars in Local Group galaxies – V. The fast and early evolution of the low-mass Eridanus II dSph galaxy
Authors: Martínez-Vázquez C E , Monelli M , Cassisi S , Taibi S , Gallart C , Vivas A K , Walker A R , Martín-Ravelo P , Zenteno A , Battaglia G , Bono G , Calamida A , Carollo D , Cicuéndez L , Fiorentino G , Marconi M , Salvadori S , Balbinot E , Bernard E J , Dall’Ora M , Stetson P B
Published: September 2021

We present a detailed study of the variable star population of Eridanus II (Eri II), an ultra-faint dwarf galaxy that lies close to the Milky Way virial radius. We analyse multi-epoch g, r, i ground-based data from Goodman and the Dark Energy Camera, plus F475W, F606W, F814W space data from the Advanced Camera for Surveys. We report the detection of 67 RR Lyrae (RRL) stars and 2 Anomalous Cepheids, most of them new discoveries. With the RRL stars, we measure the distance modulus of Eri II, μ0 = 22.84 ± 0.05 mag (D⊙ = 370 ± 9 kpc), and derive a metallicity spread of 0.3 dex (0.2 dex intrinsic). The colour distribution of the horizontal branch (HB) and the period distribution of the RRL stars can be nicely reproduced by a combination of two stellar models of [Fe/H] = (−2.62, −2.14). The overall low metallicity is consistent with the red giant branch bump location, 0.65 mag brighter than the HB. These results are in agreement with previous spectroscopic studies. The more metal-rich RRL and the RRab stars have greater central concentration than the more metal-poor RRL and the RRc stars that are mainly located outside ∼1 rh. This is similar to what is found in larger dwarf galaxies such as Sculptor, and in agreement with an outside-in galaxy formation scenario. This is remarkable in such a faint dwarf galaxy with an apparently single and extremely short (<1 Gyr) star formation burst. Finally, we have derived new and independent structural parameters for Eri II and its star cluster using our new data that are in very good agreement with previous estimates.
Probing the circumnuclear environment of NGC 1275 with high-resolution X-ray spectroscopy
Authors: Reynolds Christopher S , Smith Robyn N , Fabian Andrew C , Fukazawa Yasushi , Kara Erin A , Mushotzky Richard F , Noda Hirofumi , Tombesi Francesco , Veilleux Sylvain
Published: September 2021

NGC 1275 is the brightest cluster galaxy (BCG) in the Perseus cluster and hosts the active galactic nucleus (AGN) that is heating the central 100 kpc of the intracluster medium atmosphere via a regulated feedback loop. Here, we use a deep (490 ks) Cycle-19 Chandra High-Energy Transmission Grating (HETG) observation of NGC 1275 to study the anatomy of this AGN. The X-ray continuum is adequately described by an unabsorbed power law with photon index Γ ≈ 1.9, creating strong tension with the detected column of molecular gas seen via HCN and HCO+ line absorption against the parsec-scale core/jet. This tension is resolved if we permit a composite X-ray source; allowing a column of $N_\mathrm{ H}\sim 8\times 10^{22}\hbox{${\rm \, cm}^{-2}\, $}$ to cover ∼15 per cent of the X-ray emitter does produce a significant improvement in the statistical quality of the spectral fit. We suggest that the dominant unabsorbed component corresponds to the accretion disc corona, and the sub-dominant X-ray component is the jet working surface and/or jet cocoon that is expanding into clumpy molecular gas. We suggest that this may be a common occurrence in BCG-AGN. We conduct a search for photoionized absorbers/winds and fail to detect such a component, ruling out columns and ionization parameters often seen in many other Seyfert galaxies. We detect the 6.4 keV iron-K α fluorescence line seen previously by XMM–Newton and Hitomi. We describe an analysis methodology that combines dispersive HETG spectra, non-dispersive microcalorimeter spectra, and sensitive XMM–Newton/EPIC spectra in order to constrain (sub)arcsec-scale extensions of the iron-K α emission region.
Azimuthal propagation of star formation in nearby spiral galaxies: NGC 628, NGC 3726, and NGC 6946
Authors: Sakhibov F , Gusev A S , Hemmerich C
Published: September 2021

Star formation induced by a spiral shock wave, which in turn is generated by a spiral density wave, produces an azimuthal age gradient across the spiral arm, which has opposite signs on either side of the corotational resonance. An analysis of the spatial separation between young star clusters and nearby H ii regions has made it possible to determine the position of the corotation radius in the galaxies studied. Fourier analysis of the gas velocity field in the same galaxies independently confirmed the corotation radius estimates obtained by the morphological method presented here.
Cosmic rays and non-thermal emission in simulated galaxies – III. Probing cosmic-ray calorimetry with radio spectra and the FIR–radio correlation
Authors: Werhahn Maria , Pfrommer Christoph , Girichidis Philipp
Published: September 2021

An extinction-free estimator of the star formation rate (SFR) of galaxies is critical for understanding the high-redshift universe. To this end, the nearly linear, tight correlation of far-infrared (FIR), and radio luminosity of star-forming galaxies is widely used. While the FIR is linked to massive star formation, which also generates shock-accelerated cosmic-ray (CR) electrons and radio synchrotron emission, a detailed understanding of the underlying physics is still lacking. Hence, we perform three-dimensional magnetohydrodynamical (MHD) simulations of isolated galaxies over a broad range of halo masses and SFRs using the moving-mesh code arepo, and evolve the CR proton energy density self-consistently. In post-processing, we calculate the steady-state spectra of primary, shock-accelerated and secondary CR electrons, which result from hadronic CR proton interactions with the interstellar medium. The resulting total radio luminosities correlate with the FIR luminosities as observed and are dominated by primary CR electrons if we account for anisotropic CR diffusion. The increasing contribution of secondary emission up to 30 per cent in starbursts is compensated by the larger bremsstrahlung and Coulomb losses. CR electrons are in the calorimetric limit and lose most of their energy through inverse Compton interactions with star light and cosmic microwave background (CMB) photons while less energy is converted into synchrotron emission. This implies steep steady-state synchrotron spectra in starbursts. Interestingly, we find that thermal free–free emission flattens the total radio spectra at high radio frequencies and reconciles calorimetric theory with observations while free–free absorption explains the observed low-frequency flattening towards the central regions of starbursts.
The intermediate polar cataclysmic variable GK Persei 120 years after the nova explosion: a first dynamical mass study
Authors: Álvarez-Hernández A , Torres M A P , Rodríguez-Gil P , Shahbaz T , Anupama G C , Gazeas K D , Pavana M , Raj A , Hakala P , Stone G , Gomez S , Jonker P G , Ren J-J , Cannizzaro G , Pastor-Marazuela I , Goff W , Corral-Santana J M , Sabo R
Published: September 2021

We present a dynamical study of the intermediate polar and dwarf nova cataclysmic variable GK Persei (Nova Persei 1901) based on a multisite optical spectroscopy and R-band photometry campaign. The radial velocity curve of the evolved donor star has a semi-amplitude $K_2=126.4 \pm 0.9 \, \mathrm{km}\, \mathrm{s}^{-1}$ and an orbital period $P=1.996872 \pm 0.000009 \, \mathrm{d}$. We refine the projected rotational velocity of the donor star to $v_\mathrm{rot} \sin i = 52 \pm 2 \, \mathrm{km}\, \mathrm{s}^{-1}$ that, together with K2, provides a donor star to white dwarf mass ratio q = M2/M1 = 0.38 ± 0.03. We also determine the orbital inclination of the system by modelling the phase-folded ellipsoidal light curve and obtain i = 67° ± 5°. The resulting dynamical masses are $M_{1}=1.03^{+0.16}_{-0.11} \, \mathrm{M}_{\odot }$ and $M_2 = 0.39^{+0.07}_{-0.06} \, \mathrm{M}_{\odot }$ at 68 per cent confidence level. The white dwarf dynamical mass is compared with estimates obtained by modelling the decline light curve of the 1901 nova event and X-ray spectroscopy. The best matching mass estimates come from the nova light curve models and an X-ray data analysis that uses the ratio between the Alfvén radius in quiescence and during dwarf nova outburst.
Accurate dust temperature determination in a z = 7.13 galaxy
Authors: Bakx Tom J L C , Sommovigo Laura , Carniani Stefano , Ferrara Andrea , Akins Hollis B , Fujimoto Seiji , Hagimoto Masato , Knudsen Kirsten K , Pallottini Andrea , Tamura Yoichi , Watson Darach
Published: September 2021

We report ALMA Band 9 continuum observations of the normal, dusty star-forming galaxy A1689-zD1 at z = 7.13, resulting in a ∼4.6 σ detection at 702 GHz. For the first time, these observations probe the far-infrared spectrum shortward of the emission peak of a galaxy in the Epoch of Reionization (EoR). Together with ancillary data from earlier works, we derive the dust temperature, Td, and mass, Md, of A1689-zD1 using both traditional modified blackbody spectral energy density fitting, and a new method that relies only on the [C ii] 158 μm line and underlying continuum data. The two methods give $T_{\rm d} = (42^{+13}_{-7}, 40^{+13}_{-7}$) K, and $M_{\rm d} = (1.7^{+1.3}_{-0.7}, 2.0^{+1.8}_{-1.0})\, \times {}\, 10^{7} \, \mathrm{ M}_{\odot }$. Band 9 observations improve the accuracy of the dust temperature (mass) estimate by ∼50 per cent (6 times). The derived temperatures confirm the reported increasing Td-redshift trend between z = 0 and 8; the dust mass is consistent with a supernova origin. Although A1689-zD1 is a normal UV-selected galaxy, our results, implying that ∼85 per cent of its star-formation rate is obscured, underline the non-negligible effects of dust in EoR galaxies.
Stepwise Evolution and Exceptional Conservation of ORF1a/b Overlap in Coronaviruses
Authors: Mei Han , Kosakovsky Pond Sergei , Nekrutenko Anton
Published: September 2021

The programmed frameshift element (PFE) rerouting translation from ORF1a to ORF1b is essential for the propagation of coronaviruses. The combination of genomic features that make up PFE—the overlap between the two reading frames, a slippery sequence, as well as an ensemble of complex secondary structure elements—places severe constraints on this region as most possible nucleotide substitution may disrupt one or more of these elements. The vast amount of SARS-CoV-2 sequencing data generated within the past year provides an opportunity to assess the evolutionary dynamics of PFE in great detail. Here, we performed a comparative analysis of all available coronaviral genomic data available to date. We show that the overlap between ORF1a and ORF1b evolved as a set of discrete 7, 16, 22, 25, and 31 nucleotide stretches with a well-defined phylogenetic specificity. We further examined sequencing data from over 1,500,000 complete genomes and 55,000 raw read data sets to demonstrate exceptional conservation and detect signatures of selection within the PFE region.
Light and shade of citizen science for less charismatic invertebrate groups: quality assessment of iNaturalist nonmarine mollusc observations in central Italy
Authors: Barbato Debora , Benocci Andrea , Guasconi Mirko , Manganelli Giuseppe
Published: September 2021

Citizen science has grown in importance in recent years: many projects have been launched and records are being collected on an unprecedented scale. However, certain less charismatic invertebrate groups are still underreported and the accuracy and quality of their records in crowd-sourced citizen-science projects have rarely been investigated. Here, we used expert review to conduct quality control of nonmarine mollusc observations from central Italy on the online citizen-science platform iNaturalist (https://www.inaturalist.org/). As of December 2019, c. 400 observations of nonmarine molluscs had been reported from Tuscany on iNaturalist. Most records (59.4%) were identified to species level by the iNaturalist community and included a total of 90 taxa, providing interesting new chorological data of certain entities. Although identification of more than half the observations uploaded by the community was confirmed by expert malacologists, some major issues emerged: low quality of photographic vouchers; bias in favour of a few large common species; poor taxonomic knowledge producing incorrect identifications; and difficulty of identifying many taxa without anatomical study. Expert review remains an essential tool for verification and improvement of data quality in citizen-science projects. In this regard, information on the main diagnostic characters of the more common species (e.g. certain medium–large-sized snails and slugs) as well as tips on how to take good quality photographic images could be provided to volunteers in the form of simple guides and tutorials. High-quality training resources to support recorders and regular feedback and teamwork between scientists and citizens could prevent unverified or inaccurate records from impairing the accuracy of citizen-science datasets and offer a real opportunity to discover and conserve less charismatic taxa.
Becoming and Beyond: Applying Goethe’s Progressive and Retrogressive Metamorphosis to Fanny Hensel’s Piano Sonatas
Authors: Osborne Tyler
Published: September 2021

Over the last decade, Janet Schmalfeldt’s concept of “becoming” has provided groundwork to evaluate how ambiguous formal moments gradually come into focus through the practice of retrospective reinterpretation. I supplement Schmalfeldt’s Hegelian perspective with concepts drawn from Goethe’s botanical studies to propose a type of becoming that is not limited to retrospective reinterpretation but instead embraces gradual thematic transformations that can function either progressively or retrogressively. Using Fanny Hensel’s piano sonatas as case studies, I explain how the two categories of progressive and retrogressive metamorphosis are fitting metaphors to describe gradual thematic transformations within Romantic-era composers’ works that resist formal prototypes.
The Times are A-Changin’: Metric Flexibility and Text Expression in 1960s and 1970s Singer-Songwriter Music
Authors: Murphy Nancy
Published: September 2021

In 1960s and 1970s singer-songwriter music, some artists used a malleable approach to meter in performance that resulted in songs with extremes of self-expressive timing flexibility that cannot be accounted for by using a single conception of meter. As a solution, this article draws together theories of metric hierarchy, metrical reinterpretation, and metric process to develop the theory of flexible meter. This approach recasts meter as able to encompass the variety of metric scenarios presented by these singer-songwriters, from metric regularity to metric ambiguity and vacillations between these two possibilities. Performances by Bob Dylan, Joni Mitchell, Buffy Sainte-Marie, Paul Simon, and Cat Stevens are discussed to investigate their levels of engagement with meter—the degree to which their performances are regular or ambiguous—and how the individual metric style of each artist contributes to the self-expressive singer-songwriter performance practice.
Two coexisting pseudo-mirror heteromolecular telomeric G-quadruplexes in opposite loop progressions differentially recognized by a low equivalent of Thioflavin T
Authors: Fu Wenqiang , Jing Haitao , Xu Xiaojuan , Xu Suping , Wang Tao , Hu Wenxuan , Li Huihui , Zhang Na
Published: September 2021

The final 3′-terminal residue of the telomeric DNA G-overhang is inherently less precise. Here, we describe how alteration of the last 3′-terminal base affects the mutual recognition between two different G-rich oligomers of human telomeric DNA in the formation of heteromolecular G-quadruplexes (hetero-GQs). Associations between three- and single-repeat fragments of human telomeric DNA, target d(GGGTTAGGGTTAGGG) and probe d(TAGGGT), in Na+ solution yield two coexisting forms of (3 + 1) hybrid hetero-GQs: the kinetically favourable LLP-form (left loop progression) and the thermodynamically controlled RLP-form (right loop progression). However, only the adoption of a single LLP-form has been previously reported between the same probe d(TAGGGT) and a target variant d(GGGTTAGGGTTAGGGT) having one extra 3′-end thymine. Moreover, the flanking base alterations of short G-rich probe variants also significantly affect the loop progressions of hetero-GQs. Although seemingly two pseudo-mirror counter partners, the RLP-form exhibits a preference over the LLP-form to be recognized by a low equivalent of fluorescence dye thioflavin T (ThT). To a greater extent, ThT preferentially binds to RLP hetero-GQ than with the corresponding telomeric DNA duplex context or several other representative unimolecular GQs.
A rapid method to visualize human mitochondrial DNA replication through rotary shadowing and transmission electron microscopy
Authors: Kosar Martin , Piccini Daniele , Foiani Marco , Giannattasio Michele
Published: September 2021

We report a rapid experimental procedure based on high-density in vivo psoralen inter-strand DNA cross-linking coupled to spreading of naked purified DNA, positive staining, low-angle rotary shadowing, and transmission electron microscopy (TEM) that allows quick visualization of the dynamic of heavy strand (HS) and light strand (LS) human mitochondrial DNA replication. Replication maps built on linearized mitochondrial genomes and optimized rotary shadowing conditions enable clear visualization of the progression of the mitochondrial DNA synthesis and visualization of replication intermediates carrying long single-strand DNA stretches. One variant of this technique, called denaturing spreading, allowed the inspection of the fine chromatin structure of the mitochondrial genome and was applied to visualize the in vivo three-strand DNA structure of the human mitochondrial D-loop intermediate with unprecedented clarity.
ZFC3H1 prevents RNA trafficking into nuclear speckles through condensation
Authors: Wang Yimin , Fan Jing , Wang Jianshu , Zhu Yi , Xu Lin , Tong Deng , Cheng Hong
Published: September 2021

Controlling proper RNA pool for nuclear export is important for accurate gene expression. ZFC3H1 is a key controller that not only facilitates nuclear exosomal degradation, but also retains its bound polyadenylated RNAs in the nucleus upon exosome inactivation. However, how ZFC3H1 retains RNAs and how its roles in RNA retention and degradation are related remain largely unclear. Here, we found that upon degradation inhibition, ZFC3H1 forms nuclear condensates to prevent RNA trafficking to nuclear speckles (NSs) where many RNAs gain export competence. Systematic mapping of ZFC3H1 revealed that it utilizes distinct domains for condensation and RNA degradation. Interestingly, ZFC3H1 condensation activity is required for preventing RNA trafficking to NSs, but not for RNA degradation. Considering that no apparent ZFC3H1 condensates are formed in normal cells, our study suggests that nuclear RNA degradation and retention are two independent mechanisms with different preference for controlling proper export RNA pool—degradation is preferred in normal cells, and condensation retention is activated upon degradation inhibition.
Structural basis of transcription activation by the global regulator Spx
Authors: Shi Jing , Li Fangfang , Wen Aijia , Yu Libing , Wang Lu , Wang Fulin , Jin Yuanling , Jin Sha , Feng Yu , Lin Wei
Published: September 2021

Spx is a global transcriptional regulator in Gram-positive bacteria and has been inferred to efficiently activate transcription upon oxidative stress by engaging RNA polymerase (RNAP) and promoter DNA. However, the precise mechanism by which it interacts with RNAP and promoter DNA to initiate transcription remains obscure. Here, we report the cryo-EM structure of an intact Spx-dependent transcription activation complex (Spx–TAC) from Bacillus subtilis at 4.2 Å resolution. The structure traps Spx in an active conformation and defines key interactions accounting for Spx-dependent transcription activation. Strikingly, an oxidized Spx monomer engages RNAP by simultaneously interacting with the C-terminal domain of RNAP alpha subunit (αCTD) and σA. The interface between Spx and αCTD is distinct from those previously reported activators, indicating αCTD as a multiple target for the interaction between RNAP and various transcription activators. Notably, Spx specifically wraps the conserved –44 element of promoter DNA, thereby stabilizing Spx–TAC. Besides, Spx interacts extensively with σA through three different interfaces and promotes Spx-dependent transcription activation. Together, our structural and biochemical results provide a novel mechanistic framework for the regulation of bacterial transcription activation and shed new light on the physiological roles of the global Spx-family transcription factors.
Combinatorial assembly platform enabling engineering of genetically stable metabolic pathways in cyanobacteria
Authors: Taylor George M , Hitchcock Andrew , Heap John T
Published: September 2021

Cyanobacteria are simple, efficient, genetically-tractable photosynthetic microorganisms which in principle represent ideal biocatalysts for CO2 capture and conversion. However, in practice, genetic instability and low productivity are key, linked problems in engineered cyanobacteria. We took a massively parallel approach, generating and characterising libraries of synthetic promoters and RBSs for the cyanobacterium Synechocystis sp. PCC 6803, and assembling a sparse combinatorial library of millions of metabolic pathway-encoding construct variants. Genetic instability was observed for some variants, which is expected when variants cause metabolic burden. Surprisingly however, in a single combinatorial round without iterative optimisation, 80% of variants chosen at random and cultured photoautotrophically over many generations accumulated the target terpenoid lycopene from atmospheric CO2, apparently overcoming genetic instability. This large-scale parallel metabolic engineering of cyanobacteria provides a new platform for development of genetically stable cyanobacterial biocatalysts for sustainable light-driven production of valuable products directly from CO2, avoiding fossil carbon or competition with food production.
Integrative analysis of epigenetics data identifies gene-specific regulatory elements
Authors: Schmidt Florian , Marx Alexander , Baumgarten Nina , Hebel Marie , Wegner Martin , Kaulich Manuel , Leisegang Matthias S , Brandes Ralf P , Göke Jonathan , Vreeken Jilles , Schulz Marcel H
Published: September 2021

Understanding how epigenetic variation in non-coding regions is involved in distal gene-expression regulation is an important problem. Regulatory regions can be associated to genes using large-scale datasets of epigenetic and expression data. However, for regions of complex epigenomic signals and enhancers that regulate many genes, it is difficult to understand these associations. We present StitchIt, an approach to dissect epigenetic variation in a gene-specific manner for the detection of regulatory elements (REMs) without relying on peak calls in individual samples. StitchIt segments epigenetic signal tracks over many samples to generate the location and the target genes of a REM simultaneously. We show that this approach leads to a more accurate and refined REM detection compared to standard methods even on heterogeneous datasets, which are challenging to model. Also, StitchIt REMs are highly enriched in experimentally determined chromatin interactions and expression quantitative trait loci. We validated several newly predicted REMs using CRISPR-Cas9 experiments, thereby demonstrating the reliability of StitchIt. StitchIt is able to dissect regulation in superenhancers and predicts thousands of putative REMs that go unnoticed using peak-based approaches suggesting that a large part of the regulome might be uncharted water.
The fate of notch-1 transcript is linked to cell cycle dynamics by activity of a natural antisense transcript
Authors: Vujovic Filip , Rezaei-Lotfi Saba , Hunter Neil , Farahani Ramin M
Published: September 2021

A core imprint of metazoan life is that perturbations of cell cycle are offset by compensatory changes in successive cellular generations. This trait enhances robustness of multicellular growth and requires transmission of signaling cues within a cell lineage. Notably, the identity and mode of activity of transgenerational signals remain largely unknown. Here we report the discovery of a natural antisense transcript encoded in exon 25 of notch-1 locus (nAS25) by which mother cells control the fate of notch-1 transcript in daughter cells to buffer against perturbations of cell cycle. The antisense transcript is transcribed at G1 phase of cell cycle from a bi-directional E2F1-dependent promoter in the mother cell where the titer of nAS25 is calibrated to the length of G1. Transmission of the antisense transcript from mother to daughter cells stabilizes notch-1 sense transcript in G0 phase of daughter cells by masking it from RNA editing and resultant nonsense-mediated degradation. In consequence, nAS25-mediated amplification of notch-1 signaling reprograms G1 phase in daughter cells to compensate for the altered dynamics of the mother cell. The function of nAS25/notch-1 in integrating G1 phase history of the mother cell into that of daughter cells is compatible with the predicted activity of a molecular oscillator, slower than cyclins, that coordinates cell cycle within cell lineage.
Toward a mechanistic understanding of DNA binding by forkhead transcription factors and its perturbation by pathogenic mutations
Authors: Dai Shuyan , Qu Linzhi , Li Jun , Chen Yongheng
Published: September 2021

Forkhead box (FOX) proteins are an evolutionarily conserved family of transcription factors that play numerous regulatory roles in eukaryotes during developmental and adult life. Dysfunction of FOX proteins has been implicated in a variety of human diseases, including cancer, neurodevelopment disorders and genetic diseases. The FOX family members share a highly conserved DNA-binding domain (DBD), which is essential for DNA recognition, binding and function. Since the first FOX structure was resolved in 1993, >30 FOX structures have been reported to date. It is clear now that the structure and DNA recognition mechanisms vary among FOX members; however, a systematic review on this aspect is lacking. In this manuscript, we present an overview of the mechanisms by which FOX transcription factors bind DNA, including protein structures, DNA binding properties and disease-causing mutations. This review should enable a better understanding of FOX family transcription factors for basic researchers and clinicians.
Prophage Tracer: precisely tracing prophages in prokaryotic genomes using overlapping split-read alignment
Authors: Tang Kaihao , Wang Weiquan , Sun Yamin , Zhou Yiqing , Wang Pengxia , Guo Yunxue , Wang Xiaoxue
Published: September 2021

The life cycle of temperate phages includes a lysogenic cycle stage when the phage integrates into the host genome and becomes a prophage. However, the identification of prophages that are highly divergent from known phages remains challenging. In this study, by taking advantage of the lysis-lysogeny switch of temperate phages, we designed Prophage Tracer, a tool for recognizing active prophages in prokaryotic genomes using short-read sequencing data, independent of phage gene similarity searching. Prophage Tracer uses the criterion of overlapping split-read alignment to recognize discriminative reads that contain bacterial (attB) and phage (attP) att sites representing prophage excision signals. Performance testing showed that Prophage Tracer could predict known prophages with precise boundaries, as well as novel prophages. Two novel prophages, dsDNA and ssDNA, encoding highly divergent major capsid proteins, were identified in coral-associated bacteria. Prophage Tracer is a reliable data mining tool for the identification of novel temperate phages and mobile genetic elements. The code for the Prophage Tracer is publicly available at https://github.com/WangLab-SCSIO/Prophage_Tracer.
Focal segmental glomerulosclerosis histologic variants and renal outcomes based on nephrotic syndrome, immunosuppression and proteinuria remission
Authors: Kawaguchi Takehiko , Imasawa Toshiyuki , Kadomura Moritoshi , Kitamura Hiroshi , Maruyama Shoichi , Ozeki Takaya , Katafuchi Ritsuko , Oka Kazumasa , Isaka Yoshitaka , Yokoyama Hitoshi , Sugiyama Hitoshi , Sato Hiroshi
Published: September 2021

Background

The associations of focal segmental glomerulosclerosis (FSGS) histological variants with renal outcomes have rarely been investigated comprehensively by clinically relevant subgroups in this modern age.

Methods

Data on 304 (173 nephrotic and 131 non-nephrotic) patients with biopsy-confirmed FSGS from 2010 to 2013 were analyzed using the Japanese nationwide renal biopsy registry. The primary outcome was a composite of a 30% decline in estimated glomerular filtration rate or progression to end-stage kidney disease 5 years from the biopsy. We compared outcomes of FSGS variants according to the Columbia classification using survival analyses. Subgroup analyses were performed based on nephrotic syndrome (NS), immunosuppression and proteinuria remission (PR; proteinuria <0.3 g/day) during follow-up. Additionally, associations of NS, immunosuppression and PR with outcomes were examined for each variant.

Results

The distribution of variants was 48% (n = 145) FSGS not otherwise specified, 19% (n = 57) tip, 15% (n = 47) perihilar, 13% (n = 40) cellular and 5% (n = 15) collapsing. The outcome event occurred in 87 patients (29%). No significant differences in the outcome were found among the variants. Subgroup analyses yielded similar results. However, there was a trend toward improved outcome in patients with PR irrespective of variants [hazard ratio adjusted for histological variant and potential confounders (adjusted HR) 0.19 (95% confidence interval 0.10–0.34)]. NS was marginally associated with better outcome compared with non-NS [adjusted HR 0.50 (95% confidence interval 0.25–1.01)].

Conclusions

FSGS variants alone might not have significant impacts on the renal outcome after 5 years, while PR could be predictive of improved renal prognosis for any variant. Specific strategies and interventions to achieve PR for each variant should be implemented for better renal outcomes.
An Examination of Standardized Letters of Recommendation Rating Scales Among Neurosurgical Residency Candidates During the 2020-2021 Application Cycle
Authors: Feldman Michael J , Ortiz Alexander V , Roth Steven G , Dambrino Robert J , Yengo-Kahn Aaron M , Chitale Rohan V , Chambless Lola B
Published: September 2021

BACKGROUND

Letters of recommendation (LORs) are historically an important, though subjective, component of the neurosurgery residency application process. Standardized LORs (SLORs) were introduced during the 2020 to 2021 application cycle. The intent of SLORs is to allow objective comparison of applicants and to reduce bias.

OBJECTIVE

To examine the utility of SLORs during this application cycle. We hypothesized that “grade inflation” and poor inter-rater reliability, as described by other specialties using SLORs, would limit the utility of SLORs in their current form.

METHODS

This cross-sectional study analyzed all SLORs submitted to a single neurosurgery residency program over the 2020 to 2021 cycle. Data from 7 competency domains and the overall rating were recorded and stratified by academic category of letter writer. Inter-rater reliability was evaluated using Krippendorff's alpha.

RESULTS

One or more SLORs was submitted as part of 298 of 393 applications (76%). Approximately 58.3% of letters written by neurosurgery chairpersons rated a given applicant as being within the top 5% across all competencies. Approximately 44.4% of program director letters similarly rated applicants as amongst the top 5%, while 73.2% and 81.4% of letters by other neurosurgeons and general surgery evaluators, respectively, rated applicants in the top 5%. Inter-rater reliability was poor (<0.33) in all rating categories, including overall (α = 0.18).

CONCLUSION

The utility of the first iteration of SLORs in neurosurgery applications is undermined by significant “grade inflation” and poor inter-rater reliability. Improvements are necessary for SLORs if they are to provide meaningful information in future application cycles.
Systemic Immune-Inflammation Index Predicts Delayed Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage
Authors: Geraghty Joseph R , Lung Tyler J , Hirsch Yonatan , Katz Eitan A , Cheng Tiffany , Saini Neil S , Pandey Dilip K , Testai Fernando D
Published: September 2021

BACKGROUND

Delayed cerebral vasospasm is a feared complication of aneurysmal subarachnoid hemorrhage (SAH).

OBJECTIVE

To investigate the relationship of systemic inflammation, measured using the systemic immune-inflammation (SII) index, with delayed angiographic or sonographic vasospasm. We hypothesize that early elevations in SII index serve as an independent predictor of vasospasm.

METHODS

We retrospectively reviewed the medical records of 289 SAH patients for angiographic or sonographic evidence of delayed cerebral vasospasm. SII index [(neutrophils × platelets/lymphocytes)/1000] was calculated from laboratory data at admission and dichotomized based on whether or not the patient developed vasospasm. Multivariable logistic regression and receiver operating characteristic (ROC) analysis were performed to determine the ability of SII index to predict the development of vasospasm.

RESULTS

A total of 246 patients were included in our study, of which 166 (67.5%) developed angiographic or sonographic evidence of cerebral vasospasm. Admission SII index was elevated for SAH in patients with vasospasm compared to those without (P < .001). In univariate logistic regression, leukocytes, neutrophils, lymphocytes, neutrophil-lymphocyte ratio (NLR), and SII index were associated with vasospasm. After adjustment for age, aneurysm location, diabetes mellitus, hyperlipidemia, and modified Fisher scale, SII index remained an independent predictor of vasospasm (odds ratio 1.386, P = .003). ROC analysis revealed that SII index accurately distinguished between patients who develop vasospasm vs those who do not (area under the curve = 0.767, P < .001).

CONCLUSION

Early elevation in SII index can independently predict the development of delayed cerebral vasospasm in aneurysmal SAH.
Coagulopathy and Progression of Intracranial Hemorrhage in Traumatic Brain Injury: Mechanisms, Impact, and Therapeutic Considerations
Authors: Maegele Marc
Published: September 2021

BACKGROUND

Traumatic brain injury (TBI) remains one of the most challenging health and socioeconomic problems of our times. Clinical courses may be complicated by hemostatic abnormalities either pre-existing or developing with TBI.

OBJECTIVE

To review frequencies, patterns, mechanisms, novel approaches to diagnostics, treatment, and outcomes of hemorrhagic progression and coagulopathy after TBI.

METHODS

Selective review of the literature in the databases Medline (PubMed) and Cochrane Reviews using different combinations of the relevant search terms was conducted.

RESULTS

Of the patients, 20% with isolated TBI display laboratory coagulopathy upon hospital admission with profound effect on morbidity and mortality. Preinjury use of antithrombotic agents may be associated with higher rates of hemorrhagic progression and delayed traumatic intracranial hemorrhage. Further testing may display various changes affecting platelet function/numbers, pro- and/or anticoagulant factors, and fibrinolysis as well as interactions between brain tissues, vascular endothelium, mechanisms of inflammation, and blood flow dynamics. The nature of hemostatic disruptions after TBI remains elusive but current evidence suggests the presence of both a hyper- and hypocoagulable state with possible overlap and lack of distinction between phases and states. More “global” hemostatic assays, eg, viscoelastic and thrombin generation tests, may provide more detailed and timely information on the overall hemostatic potential thereby allowing early “goal-directed” therapies.

CONCLUSION

Whether timely and targeted management of hemostatic abnormalities after TBI can protect against secondary brain injury and thereby improve outcomes remains elusive. Innovative technologies for diagnostics and monitoring offer windows of opportunities for precision medicine approaches to managing TBI.
The Morbidity and Mortality of Surgery for Traumatic Brain Injury in Geriatric Patients: A Study of Over 100 000 Patient Cases
Authors: Haddad Alexander F , DiGiorgio Anthony M , Lee Young M , Lee Anthony T , Burke John F , Huang Michael C , Dhall Sanjay S , Manley Geoffrey T , Tarapore Phiroz E
Published: September 2021

BACKGROUND

Geriatric patients have the highest rates of Traumatic Brain Injury (TBI)-related hospitalization and death. This contributes to an assumption of futility in aggressive management in this population.

OBJECTIVE

To evaluate the effect of surgical intervention on the morbidity and mortality of geriatric patients with TBI.

METHODS

A retrospective analysis of patients ≥80 yr old with TBI from 2003 to 2016 was performed using the National Trauma Data Bank. Univariate and multivariate analyses were performed to compare outcomes between surgery and nonsurgery groups.

RESULTS

A total of 127 129 patient incidents were included: 121 185 (95.3%) without surgery and 5944 (4.7%) with surgery. The surgical group was slightly younger (84.0 vs 84.3, P < .001) and predominantly male (60.2% vs 44.4%, P < .001). Mean emergency department (ED) Glasgow Coma Scale (GCS) was lower in surgical patients (12.4 vs 13.7, P < .001). Complications (OR = 1.91, CI:1.80-2.02, P < .001) and hospital length of stay (LOS, ß = 5.25, CI:5.08-5.42, P < .001) were independently associated with surgery. Intensive care unit (ICU) LOS (ß = 3.19, CI:3.05-3.34, P < .001), ventilator days (ß = 1.57, CI:1.22-1.92, P < .001), and reduced discharge home (OR = 0.434, CI:0.400-0.470, P < .001) were also independently associated with surgery. However, surgery was not independently associated with mortality on multivariate analysis (OR = 1.03, CI:0.955-1.12, P = .423). Recursive partitioning analysis identified ED GCS and injury severity score (ISS) as prognosticators of mortality following surgical intervention.

CONCLUSION

Surgical treatment of geriatric patients with TBI is associated with increased complications, hospital LOS, ICU LOS, and ventilator days as well as reduced discharge to home. However, surgery is not associated with increased mortality. ISS and ED GCS are prognosticators of mortality following surgical intervention.
Artificially regulated synthesis of nanocrystals in live cells
Authors: Liu An-An , Sun En-Ze , Wang Zhi-Gang , Liu Shu-Lin , Pang Dai-Wen
Published: September 2021

Live cells, as reservoirs of biochemical reactions, can serve as amazing integrated chemical plants where precursor formation, nucleation and growth of nanocrystals, and functional assembly, can be carried out accurately following an artificial program. It is crucial but challenging to deliberately direct intracellular pathways to synthesize desired nanocrystals that cannot be produced naturally in cells, because the relevant reactions exist in different spatiotemporal dimensions and will never encounter each other spontaneously. This article summarizes the progress in the introduction of inorganic functional nanocrystals into live cells via the ‘artificially regulated space–time-coupled live-cell synthesis’ strategy. We also describe ingenious bio-applications of nanocrystal–cell systems, and quasi-biosynthesis strategies expanded from live-cell synthesis. Artificially regulated live-cell synthesis—which involves the interdisciplinary application of biology, chemistry, nanoscience and medicine—will enable researchers to better exploit the unanticipated potentialities of live cells and open up new directions in synthetic biology.
Reducing the Burden of Disease Through Tobacco Taxes in Mongolia: A Health Impact Analysis Using a Dynamic Public Health Model
Authors: Tuvdendorj Ariuntuya , Konings Stefan R A , Purevdorj Bolormaa , Buskens Erik , Feenstra Talitha L
Published: September 2021

Background/Objectives

Smoking is the leading risk factor for many chronic diseases. The quantitative analysis of potential health gains from reduced smoking is important for establishing priorities in Mongolia’s health policy. This study quantifies the effect of tobacco-tax increases on future smoking prevalence and the associated smoking-related burden of disease in Mongolia.

Methods

The dynamic model for health impact assessment (DYNAMO-HIA) tool was used. The most recent data were used as input for evaluating tobacco-taxation scenarios. Demographic data were taken from the Mongolian Statistical Information Services. Smoking data came from a representative population-based STEPS survey, and smoking-related disease data were obtained from the health-information database of Mongolia’s National Health Center. Simulation was used to evaluate various levels of one-time price increases on tobacco products (25% and 75%) in Mongolia. Conservative interpretation suggests that the population will eventually adjust to the higher tobacco price and return to baseline smoking behaviors.

Results

Over a three-year period, smoking prevalence would be reduced by 1.2% points, corresponding to almost 40 thousand smokers at the population level for a price increase of 75%, compared to the baseline scenario. Projected health benefits of this scenario suggest that more than 137 thousand quality adjusted of life years would be gained by avoiding smoking-related diseases within a population of three million over a 30-year period.

Discussion

Prevention through effective tobacco-control policy could yield considerable gains in population health in Mongolia. Compared to current policy, tax increases must be higher to have a significant effect on population health.

Implications

Tobacco taxation is an effective policy for reducing the harm of tobacco smoking, while benefiting population health in countries where the tobacco epidemic is still in an early stage. Smoking prevalence and smoking behaviors in these countries differ from those in Western countries. Reducing the uptake of smoking among young people could be a particularly worthwhile benefit of tobacco-tax increases.