bluuebunny/crossref_metadata_2025 huggingface dataset:
Which black hole formed first? Mass-ratio reversal in massive binary stars from gravitational-wave data
Authors: Mould Matthew , Gerosa Davide , Broekgaarden Floor S , Steinle Nathan
Published: October 2022

Population inference of gravitational-wave catalogues is a useful tool to translate observations of black hole mergers into constraints on compact-binary formation. Different formation channels predict identifiable signatures in the astrophysical distributions of source parameters, such as masses and spins. One example within the scenario of isolated binary evolution is mass-ratio reversal: even assuming efficient core–envelope coupling in massive stars and tidal spin-up of the stellar companion by the first-born black hole, a compact binary with a lighter, non-spinning first-born black hole and a heavier, spinning second-born black hole can still form through mass transfer from the initially more to less massive progenitor. Using current LIGO/Virgo observations, we measure the fraction of sources in the underlying population with this mass–spin combination and interpret it as a constraint on the occurrence of mass-ratio reversal in massive binary stars. We modify commonly used population models by including negligible-spin subpopulations and, most crucially, non-identical component spin distributions. We do not find evidence for subpopulations of black holes with negligible spins and measure the fraction of massive binary stars undergoing mass-ratio reversal to be consistent with zero and $\lt 32{{\ \rm per\ cent}}$ ($99{{\ \rm per\ cent}}$ confidence). The dimensionless spin peaks around 0.2–0.3 appear robust, however, and are yet to be explained by progenitor formation scenarios.
OGLE-BLG504.12.201843: a possible extreme dwarf nova
Authors: Landri Camille , Pejcha Ondrej , Pawlak Michał , Udalski Andrzej , Prieto Jose L , Barrientos Manuel , Strader Jay , Dong Subo
Published: October 2022

We present the analysis of existing optical photometry and new optical spectroscopy of the candidate cataclysmic variable star OGLE-BLG504.12.201843. As was shown previously, this object has an orbital period of 0.523419 d and exhibits year-long outbursts with a mean period of 973 d. Using digitized photographic archives, we show that the earliest recorded outburst occurred in 1910. We propose that this object is a U Gem-type dwarf nova (DN) with extreme properties. The orbital variability of the system in outburst shows clear signs of an accretion disc, from which the outburst likely originates. During quiescence, the object slowly brightens by up to 0.75 mag in the I band over 600 d before the outburst and exhibits small flares with amplitude ≲0.2 mag in the I band. We interpret the gradual brightening as an increase in the luminosity and temperature of the accretion disc, which is theoretically predicted but only rarely seen in DNe. The origin of small flares remains unexplained. The spectra show Balmer absorption lines both in quiescence and outburst, which can be associated with a bright secondary star or a cold accretion disc. During outbursts, emission lines with full width at half-maximum of about 450 km s−1 appear; however, they lack typical double-peaked profiles. We suggest that either these lines originate in the disc winds or the orbital inclination is low, the latter being consistent with constrains obtained from the orbital variability of the system. Due to its extreme properties and peculiarities, OGLE-BLG504.12.201843 is an excellent object for further follow-up studies.
Characterization of the NUV and optical emission and temperature of flares from Ross 733 with Swift and TESS
Authors: Jackman James A G
Published: October 2022

We present the results of a coordinated campaign to simultaneously observe the M star binary Ross 733 in the optical and near-ultraviolet (NUV) with TESS and Swift, respectively. We observed two flares in the Swift NUV light curve. One of these was decay phase of a flare that was also detected with TESS and the other was only detected in the NUV. We used the TESS light curve to measure the white-light flare rate of Ross 733, and calculate that the system flares with an energy of 1033 erg once every 1.5 d. We used our simultaneous observations to measure a pseudo-continuum temperature of $7340^{+810}_{-900}$ K during the flare decay. We also used our observations to test the NUV predictions of the 9000 K blackbody flare model, and find that it underestimates number of flares we detect in our Swift NUV light curve. We discuss the reasons for this and attribute it to the unaccounted contributions from emission lines and continuum temperatures above 9000 K. We discuss how additional observations are required to break the degeneracy between the two in future multiwavelength flare campaigns.
Bhjet: a public multizone, steady state jet + thermal corona spectral model
Authors: Lucchini M , Ceccobello C , Markoff S , Kini Y , Chhotray A , Connors R M T , Crumley P , Falcke H , Kantzas D , Maitra D
Published: October 2022

Accreting black holes are sources of major interest in astronomy, particular those launching jets because of their ability to accelerate particles, and dramatically affect their surrounding environment up to very large distances. The spatial, energy, and time-scales at which a central active black hole radiates and impacts its environment depend on its mass. The implied scale-invariance of accretion/ejection physics between black hole systems of different central masses has been confirmed by several studies. Therefore, designing a self-consistent theoretical model that can describe such systems, regardless of their mass, is of crucial importance to tackle a variety of astrophysical sources. We present here a new and significantly improved version of a scale invariant, steady-state, multizone jet model, which we rename BHJet, resulting from the efforts of our group to advance the modelling of black hole systems. We summarize the model assumptions and basic equations, how they have evolved over time, and the additional features that we have recently introduced. These include additional input electron populations, the extension to cyclotron emission in near-relativistic regime, an improved multiple inverse-Compton scattering method, external photon seed fields typical of active galactic nucleus, and a magnetically dominated jet dynamical model as opposed to the pressure-driven jet configuration present in older versions. In this paper, we publicly release the code on GitHub and, in order to facilitate the user’s approach to its many possibilities, showcase a few applications as a tutorial.
LOFAR discovery of rare large FR I jets in the low-luminosity radio galaxy NGC 5322
Authors: Omar Amitesh
Published: October 2022

The discovery of faint Fanaroff–Riley type I (FR I) radio jets in the elliptical galaxy NGC 5322 is reported here using the 144-MHz image from Data Release 2 of the Low-Frequency Array (LOFAR) Two-metre Sky Survey (LoTSS). The jets have an angular extent of ∼40 arcmin or a projected physical extent of ∼360 kpc. The faint jets remain well collimated and disappear in the intergalactic medium, without any detected hotspots or radio lobes. The relatively brighter jets, previously detected only up to the ∼21 kpc extent at higher frequencies, are within the optical extent of the galaxy. The jets become faint abruptly outside, where detection is made only in the LOFAR image. The total radio luminosity of the galaxy at 144 MHz is estimated to be (3.7 ± 0.4) × 1022 W Hz−1. The 144-MHz radio luminosity of the faint jets outside the optical extent is estimated to be (7.1 ± 2.0) × 1021 W Hz−1. The size of the jets is exceptionally large for the galaxy’s low radio luminosity, when compared with other radio galaxies. It makes NGC 5322 a rare radio galaxy, previously not detected in other radio surveys. A combined effect of stellar core depletion and low-density environment around the jets, which results in a weak entrainment of the material surrounding the jets, could be responsible for its large size despite a low radio luminosity.
Positive antiphospholipid antibodies and pulmonary embolism in a patient with adalimumab-induced lupus
Authors: Uehara Masaaki , Matsushita Shinya , Aochi Satsuki , Yamamoto Motohisa
Published: October 2022

It is known that administration of tumor necrotic factor (TNF) inhibitors induces lupus. The case of a Crohn’s disease patient who had been treated with adalimumab (ADA) and showed positive anti-DNA and antiphospholipid antibodies and developed pulmonary embolism is presented. Fortunately, early diagnosis and intervention helped her survive. Although ADA was withdrawn, the Crohn’s disease did not recur, and the autoantibodies became negative without any steroid therapy. It is important to recognise that administration of TNF inhibitors may be associated with antiphospholipid syndrome. It is necessary to perform therapeutic interventions such as TNF inhibitor withdrawal and prompt anticoagulant therapy when such pathology is suspected.
A case of pachydermaperiostosis with myelofibrosis and treatment with ruxolitinib
Authors: Deniz Rabia , Ezircan-Alay Merve
Published: October 2022

Pachydermaperiostosis (PDP) is a rare condition of connective tissue presenting with abnormal skin and skeletal findings that usually occur as a complication of an underlying disease, especially malignancies. We described a case of a patient with severe transfusion-dependent anemia and both skin and joint findings, diagnosed as PDP. The haematological assessment revealed myelofibrosis as the underlying disease, and treatment with ruxolitinib as the first-line choice was given by skipping hydroxyurea due to pancytopenia. The patient got benefits in arthralgia and amelioration of pancytopenia and a reduced spleen volume was observed, despite the negative result for JAK2 gene mutation. This is the first case of ruxolitinib being used in PDP with myelofibrosis, and it highlights the importance of evaluating PDP as not just a skin and joint problem but a result of systemic disease and individual-based treatment.
Disease mutations of human α3 Na+/K+-ATPase define extracellular Na+ binding/occlusion kinetics at ion binding site III
Authors: Moreno Cristina , Jiao Song , Yano Sho , Holmgren Miguel
Published: October 2022

Na+/K+-ATPase, which creates transmembrane electrochemical gradients by exchanging 3 Na+ for 2 K+, is central to the pathogenesis of neurological diseases such as alternating hemiplegia of childhood. Although Na+/K+-ATPase has 3 distinct ion binding sites I–III, the difficulty of distinguishing ion binding events at each site from the others hinders kinetic study of these transitions. Here, we show that binding of Na+ at each site in the human α3 Na+/K+-ATPase can be resolved using extracellular Na+-mediated transient currents. When Na+/K+-ATPase is constrained to bind and release only Na+, three kinetic components: fast, medium, and slow, can be isolated, presumably corresponding to the protein dynamics associated with the binding (or release depending on the voltage step direction) and the occlusion (or deocclusion) of each of the 3 Na+. Patient-derived mutations of residues which coordinate Na+ at site III exclusively impact the slow component, demonstrating that site III is crucial for deocclusion and release of the first Na+ into the extracellular milieu. These results advance understanding of Na+/K+-ATPase mutation pathogenesis and provide a foundation for study of individual ions’ binding kinetics.
Money and happiness: the income–happiness correlation is higher when income inequality is higher
Authors: Oishi Shigehiro , Cha Youngjae , Komiya Asuka , Ono Hiroshi
Published: October 2022

Has the income–happiness correlation changed over time? If so, what predicts such changes? We tested these questions in diverse economic, political, and cultural contexts. Drawing on nationally representative data, we found that the income–happiness correlation has increased in the USA since 1972, as GDP per capita and income inequality increased (Study 1). Study 2 examined an income–life satisfaction correlation in nationally representative surveys between 1978 and 2011 in Japan. Unlike in the USA, there was no clear increase in the income–life satisfaction correlation over time. We next examined the income–life satisfaction correlations in 16 European countries and found that on average the income–life satisfaction correlation has increased since 1970, and it was particularly high in years of high GDP per capita and high-income inequality (Study 3). Finally, we found that among Latin American countries, the income–life satisfaction correlation has, on average, decreased since 1997, as income inequality has decreased (Study 4). Over the last 5 decades, the income–happiness correlation has increased, not decreased, in the USA and several European countries. The income–happiness correlation tends to get higher when both GDP per capita and income inequality are high, whereas it tends to get lower when GDP per capita and/or income inequality are low. These findings suggest the importance of accounting for income inequality as well as national wealth in understanding the role of money in happiness.
Alethic Openness and the Growing Block Theory of Time
Authors: Hodroj Batoul , Latham Andrew J , Lee-Tory Jordan , Miller Kristie
Published: October 2022

Whatever its ultimate philosophical merits, it is often thought that the growing block theory presents an intuitive picture of reality that accords well with our pre-reflective or folk view of time, and of the past, present, and future. This is partly motivated by the idea that we find it intuitive that, in some sense, the future is open and the past closed, and that the growing block theory is particularly well suited to accommodate this being so. In this paper, we empirically investigate three claims. First, that people's intuitive or pre-reflective sense that the future is open is at least partly captured by there being truth-gaps for future contingents: what we call alethic openness. Second, that people, perhaps tacitly, believe that the fact that the future is alethically open is a reason to endorse the growing block theory; and third, that part of what explains why people tend to naively represent our world as a growing block is that they represent the future as alethically open. We found evidence in support of the first two claims. We consider the implications of these findings for several debates in the philosophy of time.
Global estimates of the fitness advantage of SARS-CoV-2 variant Omicron
Authors: van Dorp Christiaan , Goldberg Emma , Ke Ruian , Hengartner Nick , Romero-Severson Ethan
Published: October 2022

New variants of SARS-CoV-2 show remarkable heterogeneity in their relative fitness over both time and space. In this paper we extend the tools available for estimating the selection strength for new SARS-CoV-2 variants to a hierarchical, mixed-effects, renewal equation model. This formulation allows us to estimate selection effects at the global level while incorporating both measured and unmeasured heterogeneity among countries. Applying this model to the spread of Omicron in forty countries, we find evidence for very strong but very heterogeneous selection effects. To test whether this heterogeneity is explained by differences in the immune landscape, we considered several measures of vaccination rates and recent population-level infection as covariates, finding moderately strong, statistically significant effects. We also found a significant positive correlation between the selection advantage of Delta and Omicron at the country level, suggesting that other region-specific explanatory variables of fitness differences do exist. Our method is implemented in the Stan programming language, can be run on standard consumer-grade computing resources, and will be straightforward to apply to future variants.
Viral origin of eukaryotic type IIA DNA topoisomerases
Authors: Guglielmini Julien , Gaia Morgan , Da Cunha Violette , Criscuolo Alexis , Krupovic Mart , Forterre Patrick
Published: October 2022

Type II DNA topoisomerases of the family A (Topo IIAs) are present in all Bacteria (DNA gyrase) and eukaryotes. In eukaryotes, they play a major role in transcription, DNA replication, chromosome segregation, and modulation of chromosome architecture. The origin of eukaryotic Topo IIA remains mysterious since they are very divergent from their bacterial homologs and have no orthologs in Archaea. Interestingly, eukaryotic Topo IIAs have close homologs in viruses of the phylum Nucleocytoviricota, an expansive assemblage of large and giant viruses formerly known as the nucleocytoplasmic large DNA viruses. Topo IIAs are also encoded by some bacterioviruses of the class Caudoviricetes (tailed bacteriophages). To elucidate the origin of the eukaryotic Topo IIA, we performed in-depth phylogenetic analyses on a dataset combining viral and cellular Topo IIA homologs. Topo IIAs encoded by Bacteria and eukaryotes form two monophyletic groups nested within Topo IIA encoded by Caudoviricetes and Nucleocytoviricota, respectively. Importantly, Nucleocytoviricota remained well separated from eukaryotes after removing both Bacteria and Caudoviricetes from the data set, indicating that the separation of Nucleocytoviricota and eukaryotes is probably not due to long-branch attraction artifact. The topologies of our trees suggest that the eukaryotic Topo IIA was probably acquired from an ancestral member of the Nucleocytoviricota of the class Megaviricetes, before the emergence of the last eukaryotic common ancestor (LECA). This result further highlights a key role of these viruses in eukaryogenesis and suggests that early proto-eukaryotes used a Topo IIB instead of a Topo IIA for solving their DNA topological problems.
Nocardioides ochotonae sp. nov., Nocardioides campestrisoli sp. nov. and Nocardioides pantholopis sp. nov., isolated from the Qinghai–Tibet Plateau
Authors: Zhou Juan , Wang Xiaoxia , Xu Mingchao , Yang Jing , Lai Xin-He , Jin Dong , Lu Shan , Pu Ji , Yang Caixin , Zhang Sihui , Tao Yuanmeihui , Zhang Zehui , Liu Liyun , Xu Jianguo
Published: October 2022

Six Gram-stain-positive, aerobic and irregular-rod-shaped actinobacteria (ZJ1313T, ZJ1307, MC1495T, Y192, 603T and X2025) were isolated from the Qinghai–Tibet Plateau of China and were characterized using a polyphasic taxonomic method. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the six new strains formed three distinct clusters within the genus

Nocardioides

, and strains ZJ1313T and ZJ1307 were most closely related to

N. solisilvae

JCM 31492T (16S rRNA gene sequence similarity, 98.0 %), MC1495T and Y192 to

N. houyundeii

78T (98.5 %), and 603T and X2025 to

N. dokdonensis

JCM 14815T (97.6 %). The digital DNA–DNA hybridization values of strains ZJ1313T, MC1495T and 603T among each other and with type strains of their closest relatives were all below the 70 % cut-off point, but values within each pair of new strains were all higher than the threshold. The major fatty acids of these strains were iso-C16 : 0, C17 : 1
 ω8c or C18 : 1
 ω9c. MK-8(H4) was the predominant respiratory menaquinone and ʟʟ−2,6-diaminopimelic acid was the diagnostic diamino acid. All the strains shared diphosphatidylglycerol (predominant), phosphatidylglycerol, phosphatidylcholine and phosphatidylinositol as the common polar lipids, with minor difference in the types of unidentified phospholipids, glycolipids and lipids. The G+C contents based on genomic DNA of strains ZJ1313T, MC1495T and 603T were 72.5, 72.1 and 73.2 mol%, respectively. The above results suggested that strain pairs ZJ1313T/ZJ1307, MC1495T/Y192 and 603T/X2025 represent three new species of genus

Nocardioides

, for which the names Nocardioides ochotonae sp. nov. (ZJ1313T=GDMCC 4.177T=KCTC 49537T=JCM 34185T), Nocardioides campestrisoli sp. nov. (MC1495T=GDMCC 4.176T=KCTC 49536T=JCM 34307T) and Nocardioides pantholopis sp. nov. (603T=CGMCC 4.7510T=DSM 106494T) are proposed accordingly.
Brenneria tiliae sp. nov., isolated from symptomatic Tilia × moltkei and Tilia × europaea trees in the UK
Authors: Kile Helene , Arnold Dawn , Allainguilaume Joel , Denman Sandra , Brady Carrie
Published: October 2022

Several strains of a previously undescribed bacterial species were isolated from mature Tilia hybrid trees suffering from bleeding cankers at various geographic locations in the UK. The strains were Gram-negative, facultatively anaerobic, and partial sequencing of the gyrB gene revealed that the strains belong to the genus

Brenneria

with the closest phylogenetic neighbours being

Brenneria corticis

and

Brenneria nigrifluens

. Further investigation using a polyphasic approach was undertaken to determine the taxonomic position of the novel species. Phylogenies based on the 16S rRNA gene and multilocus sequence analysis of partial housekeeping gene sequences of gyrB, rpoB, infB and atpD revealed that the strains formed an independent cluster within the genus

Brenneria

. The phenotypic and chemotaxonomic assays demonstrated that the strains could be differentiated from the closest relatives. Genome analysis of representative strains revealed in silico DNA–DNA hybridization values below the threshold for species delimitation, although the average nucleotide identity values obtained when compared to

B. corticis

(95.9–96%) were slightly higher than the suggested cut-off value of 95%. However, as all other data suggests that the strains belong to a novel taxon that can be differentiated from the closest relatives, we propose that the strains represent a novel species in the genus

Brenneria

, Brenneria tiliae sp. nov. (type strain WC1b.1T=LMG 32575T=NCPPB 4697T).
Parachryseolinea silvisoli gen. nov., sp. nov., isolated from forest soil, and reclassification of Chryseolinea flava as Pseudochryseolinea flava gen. nov., comb. nov.
Authors: Wang Chunling , Lv Yingying , Li Anzhang , Yao Qing , Zhu Honghui
Published: October 2022

A lemon-chiffon strain, designated QH1ED-6-2T, was isolated from a soil sample collected from Qinghai Virgin Forests, Qinghai Province, PR China. The strain was Gram-stain-negative, aerobic, rod-shaped and motile by gliding. Phylogenetic analysis of 16S rRNA gene sequences revealed that strain QH1ED-6-2T belongs to the family

Fulvivirgaceae

, and has the highest similarity values of 93.6–92.0 % to

Ohtaekwangia koreensis

CCUG 58939T,

Ohtaekwangia kribbensis

CCUG 58938T,

Chryseolinea flava

SDU1-6T and

Chryseolinea serpens

DSM 24574T, respectively. The major cellular fatty acids included iso-C15 : 0, C16 : 1
 ω5c, iso-C17 : 0 3-OH and summed feature 3. The major polar lipid was phosphatidylethanolamine. The predominant respiratory quinone was menaquinone-7. The average amino acid identity values and percentages of conserved proteins between QH1ED-6-2T and its closely related genera were 66.4–69.6 % and 58.9–64.9 %, respectively, which are interspersed in the intra-genera cutoff values. The digital DNA–DNA hybridization values were 17.6–19.2 %. The draft genome size of strain QH1ED-6-2T was 7.98 Mbp with a DNA G+C content of 51.4 mol%. Based on phenotypic, chemotaxonomic, phylogenetic data, genomic DNA G+C content, as well as AAI, POCP and dDDH results, strain QH1ED-6-2T represents a novel species of a new genus in the family

Fulvivirgaceae

, for which the name Parachryseolinea silvisoli sp. nov. is proposed. The type strain is QH1ED-6-2T (=GDMCC 1.2318T=JCM 35041T). We also propose the reclassification of

Chryseolinea flava

as Pseudochryseolinea flava gen. nov., comb. nov. (type strain SDU1-6T=CGMCC 1.13492T=JCM 32520T).
Nonuniform structural properties of wings confer sensing advantages
Authors: Weber Alison I , Babaei Mahnoush , Mamo Amanuel , Brunton Bingni W , Daniel Thomas L , Bergbreiter Sarah
Published: October 2022

Sensory feedback is essential to both animals and robotic systems for achieving coordinated, precise movements. Mechanosensory feedback, which provides information about body deformation and position in space, depends not only on the properties of sensors but also on the structure in which they are embedded. In insects, wing structure plays a particularly important role in flapping flight: in addition to generating aerodynamic forces, wings provide mechanosensory feedback necessary for guiding flight while undergoing dramatic deformations over the course of each wingbeat. However, the role that wing structure plays in determining mechanosensory information is relatively unexplored. Insect wings exhibit characteristic stiffness gradients, with greatest stiffness at the base and leading edge and lowest stiffness at the tip of the trailing edge. Additionally, wings are subject to both aerodynamic and structural damping. The sensory consequences of stiffness gradients and damping are unknown. Here we examine how both the nonuniform stiffness profile of a wing and its damping impacts sensory performance, using finite elements analysis combined with sensor placement optimization approaches. We show that wings with nonuniform stiffness exhibit several advantages over uniform stiffness wings, resulting in higher accuracy of rotation detection and lower sensitivity to the placement of sensors on the wing. Moreover, we show that higher damping generally improves the accuracy with which body rotations can be detected. These results contribute to our understanding of the evolution of the nonuniform stiffness patterns in insect wings, as well as suggest design principles for robotic systems.
Local and regional scale mycorrhizal network assembly in an experimental prairie-pasture system
Authors: Shek Katherine L. , Dawson Hilary Rose , Maxwell Toby M. , Bomfim Barbara , Reed Paul B. , Bridgham Scott , Bohannan Brendan , Silva Lucas C.R.
Published: October 2022

Arbuscular mycorrhizal (AM) symbioses between plants and fungi are essential to the functioning of terrestrial ecosystems through maintaining soil stability, controlling nutrient cycles (e.g. C, N, P and K), and influencing competitive dynamics in plant communities. Despite the importance of AM symbioses, the ecological coassembly patterns of AM fungi-plant partners are not well characterized across environmental gradients. Further, it is unclear whether fungi forming associations with several plants of the same or different species – forming common mycorrhizal networks (CMNs) – preferentially allocate limiting resources within natural plant communities at the local-scale. We used an experimental prairie-pasture grassland system in three sites along a latitudinal gradient ranging from cool/wet to warm/dry climates to investigate how environmental conditions, local plant diversity and drought shift AM fungal composition and plant-fungal coassembly patterns across spatial scales. We show that plant-AM fungal assembly patterns are hierarchically structured, with environmental variables driving differences in AM fungal communities at the largest spatial scale (across sites), and plant host identity and diversity governing AM assembly at the local scale (within plot). Bipartite interaction networks revealed evidence for preferential partner selection between plants and fungi, while there was no evidence for nested assembly of plant-fungal partners. At the plot-level, we applied stable isotopes (13C and15N) to illustrate CMN assembly and nutritional function. There was no significant correlation between increased resource transfer among plants in a plot that shared more AM fungal partners; however, we identified specific AM fungi that were indicator taxa for increased plant isotope enrichment. Further research integrating stable isotope probing of fungal DNA in plant roots is necessary to more clearly illustrate the form and function of CMNs in grasslands under different environmental and plant diversity conditions.
MHC class Ia molecules facilitate MCK2-dependent MCMV infection of macrophages and virus dissemination to the salivary gland
Authors: Bošnjak Berislav , Henze Elisa , Lueder Yvonne , Hoang Do Kim Thi , Rezalofti Alaleh , Ritter Christiane , Schimrock Anja , Willenzon Stefanie , Georgiev Hristo , Fritz Lea , Galla Melanie , Wagner Karen , Messerle Martin , Förster Reinhold
Published: October 2022

Murine cytomegalovirus (MCMV) infection of macrophages relies on MCMV-encoded chemokine 2 (MCK2) through one or more unknown cellular receptors while infection of fibroblast occurs independent of MCK2 and is mediated by cell-expressed neuropilin 1. Applying a CRISPR screen, we now identified that the MHC-Ia/Beta-2-microglobulin (B2m) complex serves as an entry port for MCK2-mediated infection of macrophages. Further analyses revealed that MCK2-dependent infection requires expression of the MHC-Ia haplotypes H-2b and H-2d but not H-2k. The importance of the MCK2-MHC-I-pathway for primary infection and viral dissemination was highlighted by experiments with B2m-deficient mice, which lack surface expression of MHC-I molecules. In those mice, intranasally administered MCK2-proficient MCMV could not infect alveolar macrophages and subsequently failed to disseminate into the salivary glands. The identified molecular pathway used by MCMV to infect lung resident macrophages provides essential knowledge for understanding cytomegalovirus-induced pathogenesis, tissue targeting, and virus dissemination.
Apoptotic factors and mitochondrial complexes assist determination of strain-specific susceptibility of mice to Parkinsonian neurotoxin MPTP
Authors: Yarreiphang Haorei , Vidyadhara D J , Nambisan Anand Krishnan , Raju Trichur R , Sagar BK Chandrashekar , Alladi Phalguni Anand
Published: October 2022

Identification of genetic mutations in Parkinson’s disease (PD) promulgates the genetic nature of disease susceptibility. Resilience-associated genes being unknown till date, the normal genetic makeup of an individual may be determinative too. Our earlier studies comparing the substantia nigra (SN) and striatum of C57BL/6J, CD-1 mice and their F1-crossbreds demonstrated neuroprotective role of admixing, against the neurotoxin MPTP. Further, the differences in levels of mitochondrial fission/fusion proteins in the SN of parent strains, imply effect on mitochondrial biogenesis. Our present investigations suggest that the baseline levels of apoptotic factors Bcl-2, Bax and AIF differ across the three strains and, are differentially altered in SN following MPTP-administration. The reduction in complex-I levels exclusively in MPTP-injected C57BL/6J, reiterate mitochondrial involvement in PD pathogenesis. The MPTP-induced increase in complex-IV, in the nigra of both parent strains may be compensatory in nature. Ultrastructural evaluation showed fairly preserved mitochondria in the dopaminergic neurons of CD-1 and F1-crossbreds. However, in CD-1, the endoplasmic reticulum demonstrated distinct luminal enlargement, bordering onto ballooning, suggesting proteinopathy as a possible initial trigger.

The increase in α-synuclein in the pars reticulata of crossbreds suggests a supportive role for this output nucleus in compensating for the lost function of pars compacta. Alternatively, since α-synuclein over-expression occurs in different brain regions in PD, the α-synuclein increase here may suggest similar pathogenic outcome. Further understanding is required to resolve this biological contraption. Nevertheless, admixing reduces the risk to MPTP by favouring anti-apoptotic consequences. Similar neuroprotection may be envisaged in the admixed populace of Anglo-Indians.
ANDROMEDA by Prosilico Software Successfully Predicts Human Clinical Pharmacokinetics of 300 Drugs Out of Reach forIn VitroMethods
Authors: Fagerholm Urban , Hellberg Sven , Alvarsson Jonathan , Spjuth Ola
Published: October 2022

Abstract

Introduction

In vitromeasurements and predictions of human clinical pharmacokinetics (PK) are sometimes hindered and made impossible due to factors such as extensive binding to materials, low methodological sensitivity and large variability.

Methods

The objective was to find compounds out of reach forin vitroPK-methods and (if possible) predict corresponding human clinical estimates using the ANDROMEDA by Prosilico software.In vitromethods selected for the investigation were human microsomes and hepatocytes for measuring and predicting intrinsic hepatic metabolic clearance (CLint), Caco-2 and Ralph Russ canine kidney cells (RRCK) cells for measuring apparent intestinal permeability (Papp) for prediction of fraction absorbed (fa), plasma for measurement and estimation of unbound fraction (fu), and water and buffers for measuring solubility (S) for prediction ofin vivodissolution potential (fdiss).

Results and Conclusion

As many as 329 non-quantifiablein vitroPK-measurements for 300 compounds were found in the literature: 191 for CLint, 101 for Papp, 11 for fuand 26 for S. ANDROMEDA was successful in predicting all corresponding clinical PK-estimates for the selection of compounds with non-quantifiablein vitroPK, and predicted estimates (1.6-fold median prediction error; n=159) were generally in line with observedin vivodata and results/problems atin vitrolaboratories. Thus, ANDROMEDA is applicable for predicting human clinical PK for compounds out of reach for laboratory methods.
Sprague-Dawley rats differ in responses to medial perforant path paired pulse and tetanic activation as a function of sex and age
Authors: Walling Susan G. , Harley Carolyn W. , Martin Gerard M , Dutton Olivia DE , Burke Alexander T , Chirinos Ella A
Published: October 2022

Network plasticity in the medial perforant path (MPP) of adult (5-9 mo) and aged (18-20 mo) urethane-anesthetized male and female Sprague-Dawley rats was characterized. Paired pulses probed recurrent networks before and after a moderate tetanic protocol.

Adult females exhibited greater EPSP-spike coupling suggesting greater intrinsic excitability than adult males. Aged rats did not differ in EPSP-spike coupling but aged females had larger spikes at high currents than males. Paired pulses suggested lower GABA-B inhibition in females.

Absolute population spike measures were larger post-tetani in female rats than male rats. Relative population spike increases were greatest in adult males relative to females and to aged males. EPSP slope potentiation was detected with normalization in some post-tetanic intervals for all groups except aged males. Tetani shortened spike latency across groups.

Tetani-associated NMDA-mediated burst depolarizations were larger for the first two trains in each tetanus in adult males than other groups. EPSP slopes over 30 min post-tetani predicted spike size in female rats, but not in males.

Replicating newer evidence MPP plasticity in adult males was mediated by increased intrinsic excitability. Female MPP plasticity was related to synaptic drive increases, not excitability increases. Aged male rats were deficient in MPP plasticity.
Ketone body metabolism declines with age in mice in a sex-dependent manner
Authors: Eap Brenda , Nomura Mitsunori , Panda Oishika , Garcia Thelma Y , King Christina D , Rose Jacob P , Leone Teresa C , Kelly Daniel P , Schilling Birgit , Newman John C
Published: October 2022

Understanding how our cells maintain energy homeostasis has long been a focus of aging biology. A decline in energy metabolism is central to many age-related diseases such as Alzheimer’s disease, heart failure, frailty, and delirium. Intervening on pathways involved in energy homeostasis can extend healthy lifespan. When the primary energy substrate glucose is scarce, mice and humans can partially switch cellular energetic needs to fat-derived ketone bodies (i.e., beta-hydroxybutyrate (BHB), acetoacetate, acetone). Aging is associated with glucose intolerance and insulin insensitivity, yet, surprisingly, what role ketone body metabolism might play in compensating for impaired glucose utilization in age-related diseases is understudied. Here, we investigate how endogenous ketone body production and utilization pathways are modulated by age across the lifespan of male and female C57BL/6N mice (3 mo old, 12 mo old, 22 mo old). We show how different ages have different metabolic and gene expression responses to 1-week ketogenic diet (KD). We hypothesized that there would be a compensatory ketogenic response with age but instead saw declines in plasma BHB concentrations under fasting and non-fasting conditions with strong sexual dimorphism. Under KD, both sexes increased BHB concentrations at all ages, but only males showed strong gene expression induction. We also observed tissue-specific changes with age in baseline ketone metabolism, and surprising induction of extrahepatic ketogenic genes under KD. We found significant residual blood concentrations of BHB in KD even after a knockout of liver BHB production. Overall, these findings show that older mice have impaired non-fasting ketogenesis but are capable of increasing their ketogenic capacity under stimulation (i.e., KD) to meet energetic demands in aging. Therapies to augment non-fasting ketogenesis or provide exogenous ketones may be useful to improve energy homeostasis in diseases and conditions of aging.
LapTrack: Linear assignment particle tracking with tunable metrics
Authors: Fukai Yohsuke T. , Kawaguchi Kyogo
Published: October 2022

Motivation

Particle tracking is an important step of analysis in a variety of scientific fields, and is particularly indispensable for the construction of cellular lineages from live images. Although various supervised machine learning methods have been developed for cell tracking, the diversity of the data still necessitates heuristic methods that require parameter estimations from small amounts of data. For this, solving tracking as a linear assignment problem (LAP) has been widely applied and demonstrated to be efficient. However, there has been no implementation that allows custom connection costs, parallel parameter tuning with ground truth annotations, and the functionality to preserve ground truth connections, limiting the application to datasets with partial annotations.

Results

We developed LapTrack, a LAP-based tracker which allows including arbitrary cost functions and inputs, parallel parameter tuning, and ground-truth track preservation. Analysis of real and artificial datasets demonstrates the advantage of custom metric functions for tracking score improvement. The tracker can be easily combined with other Python-based tools for particle detection, segmentation, and visualization.

Availability and implementation

LapTrack is available as a Python package on PyPi, and the notebook examples are shared athttps://github.com/yfukai/laptrack. The data and code for this publication are hosted athttps://github.com/NoneqPhysLivingMatterLab/laptrack-optimization.

Contact

ysk@yfukai.net
Direct estimation of genome mutation rates from pedigrees in free-ranging baleen whales
Authors: Suárez-Menéndez Marcos , Bérubé Martine , Furni Fabrício , Rivera-León Vania E. , Heide-Jørgensen Mads-Peter , Larsen Finn , Sears Richard , Ramp Christian , Eriksson Britas Klemens , Etienne Rampal S. , Robbins Jooke , Palsbøll Per J.
Published: October 2022

Current low germline mutation rate (μ) estimates in baleen whales have greatly influenced research ranging from assessments of whaling impacts to evolutionary cancer biology. However, the reported rates were subject to methodological errors and uncertainty. We estimated μ directly from pedigrees in natural populations of four baleen whale species and the results were similar to primates. The implications of revised μ values include pre-exploitation population sizes at 14% of previous genetic diversity-based estimates and the conclusion that μ in itself is insufficient to explain low cancer rates in gigantic mammals (i.e., Peto’s Paradox). We demonstrate the feasibility of estimating μ from whole genome pedigree data in natural populations, which has wide-ranging implications for the many ecological and evolutionary inferences that rely on μ.
Environmental transcriptomics under heat stress: Can environmental RNA reveal changes in gene expression of aquatic organisms?
Authors: Hechler Robert M. , Yates Matthew C. , Chain Frédéric J. J. , Cristescu Melania E.
Published: October 2022

To safeguard biodiversity in a changing climate, we require taxonomic information about species turnover and insights into the health of organisms. Environmental DNA approaches are increasingly used for species identification, but cannot provide functional insights. Transcriptomic methods reveal the physiological states of macroorganisms, but are currently species specific and require tissue sampling or animal sacrifice, making community-wide assessments challenging. Here, we test if broad functional information (expression level of the transcribed genes) can be harnessed from environmental RNA (eRNA), which includes extra-organismal RNA from macroorganisms along with whole microorganisms. We exposedDaphnia pulexas well as phytoplankton prey and microorganism colonizers to control (20 °C) and heat stress (28 °C) conditions for seven days. We sequenced eRNA from tank water (after complete removal ofDaphnia) as well as RNA fromDaphniatissue, enabling comparisons of extra-organismal and organismal RNA based gene expression profiles. Both RNA types detected similar heat stress responses ofDaphnia. Using eRNA, we identified 32Daphniagenes to be differentially expressed following heat stress. Of these, 17 were also differentially expressed and exhibited similar levels of relative expression in organismal RNA. In addition to the extra-organismalDaphniaresponse, eRNA detected community-wide heat stress responses consisting of distinct functional profiles and 121 differentially expressed genes across 8 taxa. Our study demonstrates that environmental transcriptomics based on eRNA can non-invasively reveal gene expression responses of macroorganisms following environmental changes, with broad potential implications for the biomonitoring of ecological health across the trophic chain.
Nicotine enhances intravenous self-administration of cannabinoids in adult rats
Authors: Stringfield Sierra J. , Sanders Bryson E. , Suppo Jude A. , Sved Alan F. , Torregrossa Mary M.
Published: October 2022

Introduction

Nicotine and cannabis are commonly used together, yet few studies have investigated the effects of concurrent administration of both drugs. Nicotine exhibits reinforcement enhancing effects by promoting the reinforcing properties of stimuli including other drugs. As many studies of this effect have used non-contingent nicotine, we implemented a dual-self-administration model where rats are given simultaneous access to two drugs and choose which to self-administer throughout a session. Here, we investigated the effect of self-administered or non-contingently delivered nicotine on cannabinoid self-administration.

Methods

Adult male rats were allowed to self-administer the synthetic cannabinoid WIN 55,212-2 (WIN) intravenously, with or without subcutaneous nicotine injections before each session. A separate group of animals were allowed to self-administer WIN, nicotine, or saline using a dual-catheter procedure, where each solution was infused independently and associated with a separate operant response. A third group of male and female rats were allowed to self-administer delta-9-tetrahydrocannabinol (THC) with or without pre-session injections of nicotine.

Results

Nicotine injections increased self-administration of WIN and THC. During dual self-administration, nicotine availability increased saline and WIN infusions but nicotine intake was not changed by WIN or saline availability. Rats preferred nicotine over saline, but preferred nicotine and WIN equally when both were available. The effect of nicotine on cannabinoid self-administration was acute and reversible when nicotine was no longer present.

Conclusions

These results expand our understanding of the ability of nicotine to enhance reinforcement of other drugs of abuse and suggest that co-use of nicotine and cannabinoids promotes cannabinoid use in excess of what would be taken alone.

Implications

This study utilizes a dual intravenous self-administration model to investigate the ability of nicotine to enhance cannabinoid intake. Our results demonstrate that the reinforcement enhancing properties of nicotine on drug use extend to include cannabinoids, but that this effect occurs specifically when nicotine is administered alongside the cannabinoid. Interestingly, cannabinoid use did not promote nicotine intake, suggesting this mechanism of reinforcement is specific to nicotine.
A switch in jaw form-function coupling during the evolution of mammals
Authors: Tseng Z. Jack , Garcia-Lara Sergio , Flynn John J. , Holmes Emily , Rowe Timothy B. , Dickson Blake V.
Published: October 2022

The evolutionary shift from a single-element ear, multi-element jaw to a multi-element ear, single-element jaw during the transition to crown mammals marks one of the most dramatic structural transformations in vertebrates. Research on this transformation has focused on mammalian middle-ear evolution, but a mandible comprised of only the dentary is equally emblematic of this evolutionary radiation. Here we show that the remarkably diverse jaw shapes of crown mammals are coupled with surprisingly stereotyped jaw stiffness. This strength-based morphofunctional regime has a genetic basis and allowed mammalian jaws to effectively resist deformation as they radiated into highly disparate forms with markedly distinct diets. The main functional consequences for the mandible of decoupling hearing and mastication were a trade-off between higher jaw stiffness versus decreased mechanical efficiency and speed compared to non-mammals. This fundamental and consequential shift in jaw form-function underpins the ecological and taxonomic diversification of crown mammals.
Indigenous Cultural Safety Training for Applied Health, Social Work and Education Professionals: A PRISMA Scoping Review
Authors: MacLean Tammy , Qiang Jinfan , Henderson Lynn , Bowra Andrea , Howard Lisa , Pringle Victoria , Butsang Tenzin , Rice Emma , Di Ruggiero Erica , Mashford-Pringle Angela
Published: October 2022

Background

Anti-Indigenous racism is a widespread social problem in health, social work, and education systems in English-speaking Colonized countries such as Canada, with profound negative impacts to the health and education of Indigenous peoples. In 2015, Canada’s Truth and Reconciliation Commission recognized the legacy and impact of Colonization and recommended training programs for these professions on cultural competency and curricula, and on the colonial history of Canada. Yet there is little evidence on best practices for such training, highlighting the need to synthesize existing findings on how these training programs are developed, implemented, and evaluated.

Methods

This scoping review explored the academic literature on Indigenous cultural safety and competence training in the health, social work, and education fields. Medline, EMBASE, CINAHL, ERIC and ASSIA were searched for articles published between 1996-2020 in Canada, United States, Australia, and New Zealand. The Joanna Briggs Institute’s three-step search strategy was used as was the PRISMA extension for Scoping Reviews. Data was charted and synthesized in three stages.

Results

134 were included in this review. Data was extracted on four themes: 1) Article Characteristic; 2) Cultural Safety Concepts, Critiques and Rationale; 3) Characteristics of Cultural Safety Training; and 4) Evaluation Details of Cultural Safety Training. Findings suggest that research on cultural safety training programs in health, social work and education has grown significantly. Nursing and medicine professions have received a significant proportion of cultural training programs, compared with general/allied health, social work, and education. Across fields, professionals and students were targeted equally by training programs. Only half of evaluations of cultural safety and related intervention identified methodological limitations.

Implications

Considering, comparing, and contrasting literature on cultural safety and related concepts and how they are applied in practice would advance this scholarly work, as would more robust evaluations of cultural safety and similar training interventions to understand their impact at the individual level. Finally, commitment to meaningfully engage Indigenous communities to develop, implement and evaluate such programs is urgently needed.