bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimization of lead compounds into on-demand, nonhormonal contraceptives: leveraging a public–private drug discovery institute collaboration†
Authors: Balbach Melanie , Fushimi Makoto , Huggins David J , Steegborn Clemens , Meinke Peter T , Levin Lonny R , Buck Jochen
Published: April 2020

Efforts to develop new male or female nonhormonal, orally available contraceptives assume that to be effective and safe, targets must be (1) essential for fertility; (2) amenable to targeting by small-molecule inhibitors; and (3) restricted to the germline. In this perspective, we question the third assumption and propose that despite its wide expression, soluble adenylyl cyclase (sAC: ADCY10), which is essential for male fertility, is a valid target. We hypothesize that an acute-acting sAC inhibitor may provide orally available, on-demand, nonhormonal contraception for men without adverse, mechanism-based effects. To test this concept, we describe a collaboration between academia and the unique capabilities of a public-private drug discovery institute.
Determination of Gemcitabine in Plasma of Bladder Cancer Patients by Hydrophilic Interaction Chromatography with Ultraviolet Detection
Authors: Wang Meng , Hiraki Ryoichi , Nakamura Norihiro , Hayama Tadashi , Yasuda Takuji , Miyata Yasuyoshi , Sakai Hideki , Nakashima Mihoko N , Nakashima Mikiro , Ohyama Kaname
Published: April 2020

Gemcitabine is a deoxycytidine analog that has been used for a broad spectrum of tumor, such as nonsmall-cell lung cancer, bladder cancer and pancreatic cancer. Because gemcitabine is hydrophilic, hydrophilic interaction liquid chromatography (HILIC), where analytes are retained on a polar column according to their hydrophilicity, should be adequate for separation analysis of gemcitabine. In the present study, we proposed a hydrophilic interaction chromatography with ultraviolet (HILIC-UV) method with liquid–liquid extraction and adding tetrahydrouridine to plasma samples for gemcitabine analysis of clinical samples with respect to daily and wide usage. The method successfully determined gemcitabine in 56 plasma samples of 30 unique patients. Mean plasma concentration of gemcitabine was 15.0 ± 6.0 μg/mL (mean ± standard deviation). The concentration range is consistent with the data from previous literatures. Our proposed HILIC-UV method is simple and easy handling, and is widely and clinically usable for determination of gemcitabine in human plasma.
Circulating plasma concentrations of angiotensin-converting enzyme 2 in men and women with heart failure and effects of renin–angiotensin–aldosterone inhibitors
Authors: Sama Iziah E , Ravera Alice , Santema Bernadet T , van Goor Harry , ter Maaten Jozine M , Cleland John G F , Rienstra Michiel , Friedrich Alex W , Samani Nilesh J , Ng Leong L , Dickstein Kenneth , Lang Chim C , Filippatos Gerasimos , Anker Stefan D , Ponikowski Piotr , Metra Marco , van Veldhuisen Dirk J , Voors Adriaan A
Published: April 2020

Aims

The current pandemic coronavirus SARS-CoV-2 infects a wide age group but predominantly elderly individuals, especially men and those with cardiovascular disease. Recent reports suggest an association with use of renin–angiotensin–aldosterone system (RAAS) inhibitors. Angiotensin-converting enzyme 2 (ACE2) is a functional receptor for coronaviruses. Higher ACE2 concentrations might lead to increased vulnerability to SARS-CoV-2 in patients on RAAS inhibitors.

Methods and results

We measured ACE2 concentrations in 1485 men and 537 women with heart failure (index cohort). Results were validated in 1123 men and 575 women (validation cohort).

The median age was 69 years for men and 75 years for women. The strongest predictor of elevated concentrations of ACE2 in both cohorts was male sex (estimate = 0.26, P < 0.001; and 0.19, P < 0.001, respectively). In the index cohort, use of ACE inhibitors, angiotensin receptor blockers (ARBs), or mineralocorticoid receptor antagonists (MRAs) was not an independent predictor of plasma ACE2. In the validation cohort, ACE inhibitor (estimate = –0.17, P = 0.002) and ARB use (estimate = –0.15, P = 0.03) were independent predictors of lower plasma ACE2, while use of an MRA (estimate = 0.11, P = 0.04) was an independent predictor of higher plasma ACE2 concentrations.

Conclusion

In two independent cohorts of patients with heart failure, plasma concentrations of ACE2 were higher in men than in women, but use of neither an ACE inhibitor nor an ARB was associated with higher plasma ACE2 concentrations. These data might explain the higher incidence and fatality rate of COVID-19 in men, but do not support previous reports suggesting that ACE inhibitors or ARBs increase the vulnerability for COVID-19 through increased plasma ACE2 concentrations.
Association of depression and anxiety with adherence in primary care patients with heart failure—cross-sectional results of the observational RECODE-HF cohort study
Authors: Eisele Marion , Harder Malte , Rakebrandt Anja , Boczor Sigrid , Marx Gabriella , Blozik Eva , Träder Jens-Martin , Störk Stefan , Herrmann-Lingen Christoph , Scherer Martin
Published: April 2020

Background

Psychological distress has a negative impact on the prognosis and quality of life for patients with heart failure. We investigated the association between psychological distress and the patients’ adherence to medical treatment (medication adherence) and self-care advice (lifestyle adherence) in heart failure. We further examined whether there are different factors associated with low medication compared to low lifestyle adherence.

Method

This secondary analysis of the RECODE-HF cohort study analyzed baseline data of 3099 primary care heart failure patients aged 74 ± 10 years, 44.5 % female. Using multivariable regression, factors relating to medication and lifestyle adherence were investigated in order to estimate the extent to which these factors confound the association between psychological distress and adherence.

Results

Psychological distress was significantly associated with poorer medication adherence but not with lifestyle adherence after controlling for confounders. We identified different factors associated with medication compared to lifestyle adherence. A higher body mass index, a less developed social network, living alone, fewer chronic co-morbidities and unawareness of the heart failure diagnosis were only related to lower lifestyle adherence. Higher education was associated with poorer medication adherence. Male sex, younger age, lower self-efficacy and less familiar relation with the general practitioner were common factors associated with both lower medication and lifestyle adherence.

Conclusion

Promising factors for increasing medication adherence (reduction of psychological distress) and lifestyle adherence (explaining the patient his/her heart failure diagnosis more than once and increase in the patients’ self-efficacy), which were found in this cross-sectional study, must be further investigated in longitudinal studies.
Biodiversity and dairy traits of lactic acid bacteria from foliage of aromatic plants before and after dehydration process monitored by a smart sensors system
Authors: Gaglio Raimondo , Catania Pietro , Orlando Santo , Vallone Mariangela , Moschetti Giancarlo , Settanni Luca
Published: April 2020

The main hypothesis of this work was to evaluate the presence of lactic acid bacteria (LAB) intrinsically resistant to plant essential oils in sage (Salvia officinalis L.) and laurel (Laurus nobilis), for future applications in functional cheese production by addition of aromatic herbs. The effect of the drying process on the viability of LAB was evaluated with three biomass densities (3, 4 and 5 kg/m2). The drying densities did not affect weight loss, but influenced the levels of LAB of sage and laurel. A total of 10 different strains of Enterococcus faecium, Enterococcus mundtii, Enterococcus raffinosus and Leuconostoc mesenteroides were identified from laurel, while sage did not host any LAB species. In particular, L. mesenteroides was the only species sensitive to the heat treatment. Only five strains, all enterococci, were resistant to at least one antibiotic, even though no strain showed gelatinase or haemolytic activity. The investigation on the technological traits useful in cheese making demonstrated that all LAB can be considered non starter LAB, because they were characterized by a slow acidification capacity (the pH was still above 6.00 after 3 d) and a very limited autolysis (the maximum decrease of the optical density at 599 nm was barely 0.2).
Microbiome-Based Biomarkers for IBD
Authors: Ananthakrishnan Ashwin N
Published: April 2020

Crohn disease and ulcerative colitis are complex immune-mediated diseases that are characterized by a heterogeneity in presentation and clinical course. Although various clinical covariates predict adverse outcomes in these patients, they are insufficiently informative. The gut microbiome likely plays a central role in the pathogenesis of these diseases. Consequently, microbiome-based biomarkers may play an important role in risk stratification and disease prediction. Initial cross-sectional studies showed a reduced gut microbial diversity in patients with Crohn disease or ulcerative colitis, a depletion of phyla with anti-inflammatory effects such as those belonging to Firmicutes, and an increased abundance of potentially pathogenic bacteria in specific disease phenotypes. Subsequent studies longitudinally tracking microbial changes and clinical outcomes have shown dynamic changes correlating with or predictive of disease activity and resistance to therapy. The development of multicenter cohorts using harmonized protocols is essential to robustly validate these biomarkers and facilitate the integration of their evaluation into clinical practice.
Nonlinear interactions of nearly non-dispersive equatorial shallow-water waves
Authors: Wang Mian , Wang Zhan , Hajduk Hennes
Published: April 2020

This paper is concerned with nonlinear interactions of fundamental equatorial modes. In order to understand the mechanism of large-scale atmospheric motions in the near equator regime—especially the observed wavenumber-frequency spectrum—we develop novel models describing interactions among Kelvin, Yanai and Poincaré waves. Based on the methods of multiple scales and Galerkin projection, the primitive equations can be simplified to model equations which reduce the complexity and cost of computation significantly. Subsequently, the detailed numerical results indicate that wave interactions between the aforementioned modes in the non-dispersive regime depends on initial amplitude and relative phase and that the eastward Yanai wave can be generated from the second Poincaré mode. We also compare the simplified models to an advanced finite element approximation for the primitive equations. The fact that results of the latter are in good agreement, at least qualitatively, with those of the simplified models, indicates that reduced models capture most of the wave interaction mechanisms in the nearly non-dispersive regime.
When, Who, and How to Sample: Designing Practical Surveillance for 7 Neglected Tropical Diseases as We Approach Elimination
Authors: Toor Jaspreet , Coffeng Luc E , Hamley Jonathan I D , Fronterre Claudio , Prada Joaquin M , Castaño M Soledad , Davis Emma L , Godwin William , Vasconcelos Andreia , Medley Graham F , Hollingsworth T Déirdre
Published: April 2020

As neglected tropical disease programs look to consolidate the successes of moving towards elimination, we need to understand the dynamics of transmission at low prevalence to inform surveillance strategies for detecting elimination and resurgence. In this special collection, modelling insights are used to highlight drivers of local elimination, evaluate strategies for detecting resurgence, and show the importance of rational spatial sampling schemes for several neglected tropical diseases (specifically schistosomiasis, soil-transmitted helminths, lymphatic filariasis, trachoma, onchocerciasis, visceral leishmaniasis, and gambiense sleeping sickness).
The origin, fate and function of macrophages in the peripheral nervous system—an update
Authors: Amann Lukas , Prinz Marco
Published: April 2020

The field of macrophage biology has made enormous progress over recent years. This was triggered by the advent of several new techniques such as the establishment of Cre/loxP-based transgenic mouse models that allowed for the first time delineation of the ontogeny and function of specific macrophage populations across many tissues. In addition, the introduction of new high-throughput technologies like bulk RNA sequencing and later single-cell RNA sequencing as well as advances in epigenetic analysis have helped to establish gene expression profiles, enhancer landscapes and local signaling cues that define and shape the identity of diverse macrophage populations. Nonetheless, some macrophage populations, like the ones residing in the peripheral nervous system (PNS), have not been studied in such detail yet. Here, we discuss recent studies that shed new light on the ontogeny, heterogeneity and gene expression profiles of resident macrophages in peripheral nerves and described differential activation of macrophage subsets during and after acute sciatic nerve injury.
In vitro interaction of isavuconazole and anidulafungin against azole-susceptible and azole-resistant Aspergillus fumigatus isolates
Authors: Buil J B , Brüggemann R J M , Bedin Denardi L , Melchers W J G , Verweij P E
Published: April 2020

Background

The voriconazole and echinocandin combination has been found to be synergistic in vitro and in vivo against most Aspergillus fumigatus isolates, both with a WT azole phenotype and an azole-resistant phenotype. The interaction between isavuconazole and echinocandins is less well studied. This is especially true for azole-resistant isolates.

Objectives

We investigated the in vitro interaction between isavuconazole and anidulafungin for 30 A. fumigatus isolates including 18 azole-resistant isolates with various isavuconazole resistance phenotypes.

Methods

The isavuconazole/anidulafungin interaction was studied by using an adapted EUCAST-based 2D (12 × 8) chequerboard broth microdilution colorimetric assay using XTT. The interaction was analysed by FIC index (FICi) analysis and Bliss independence (BI) interaction analysis.

Results

Both the FICi analysis and the BI analysis showed synergistic interaction between isavuconazole and anidulafungin for the majority of WT and azole-resistant isolates. As we did not see significant beneficial effects of combination therapy in TR46/Y121F/T289A isolates at clinically achievable drug concentrations, it is unlikely that TR46/Y121F/T289A infections would benefit from isavuconazole and anidulafungin combination therapy.

Conclusions

In regions with high azole resistance rates this combination may benefit patients with WT disease, azole-resistant invasive aspergillosis and those with mixed azole-susceptible and azole-resistant infection, but may not be beneficial for aspergillosis due to isolates with high isavuconazole resistance, such as TR46/Y121F/T289A isolates.
Analysis of four complete linkage sequence variants within a novel lncRNA located in a growth QTL on chromosome 1 related to growth traits in chickens
Authors: Li Wenya , Jing Zhenzhu , Cheng Yingying , Wang Xiangnan , Li Donghua , Han Ruili , Li Wenting , Li Guoxi , Sun Guirong , Tian Yadong , Liu Xiaojun , Kang Xiangtao , Li Zhuanjian
Published: April 2020

An increasing number of studies have shown that quantitative trait loci (QTLs) at the end of chromosome 1 identified in different chicken breeds and populations exert significant effects on growth traits in chickens. Nevertheless, the causal genes underlying the QTL effect remain poorly understood. Using an updated gene database, a novel lncRNA (named LncFAM) was found at the end of chromosome 1 and located in a growth and digestion QTL. This study showed that the expression level of LncFAM in pancreas tissues with a high weight was significantly higher than that in pancreas tissues with a low weight, which indicates that the expression level of LncFAM was positively correlated with various growth phenotype indexes, such as growth speed and body weight. A polymorphism screening identified four polymorphisms with strong linkage disequilibrium in LncFAM: a 5-bp indel in the second exon, an A/G base mutation, and 7-bp and 97-bp indels in the second intron. A study of a 97-bp insertion in the second intron using an F2 chicken resource population produced by Anka and Gushi chickens showed that the mutant individuals with genotype II had the highest values for body weight (BW) at 0 days and 2, 4, 6, 8, 10 and 12 weeks, shank girth (SG) at 4, 8 and 12 weeks, chest width (CW) at 4, 8 and 12 weeks, body slant length (BSL) at 8 and 12 weeks, and pelvic width (PW) at 4, 8 and 12 weeks, followed by ID and DD genotypes. The amplification and typing of 2,716 chickens from ten different breeds, namely, the F2 chicken resource population, dual-type chickens, including Xichuan black-bone chickens, Lushi green-shell layers, Dongxiang green-shell layers, Changshun green-shell layers, and Gushi chickens, and commercial broilers, including Ross 308, AA, Cobb and Hubbard broilers, revealed that II was the dominant genotype. Interestingly, only genotype II existed among the tested populations of commercial broilers. Moreover, the expression level in the pancreas tissue of Ross 308 chickens was significantly higher than that in the pancreas tissue of Gushi chickens (P < 0.001), which might be related to the conversion rates among different chickens. The prediction and verification of the target gene of LncFAM showed that LncFAM might regulate the expression of its target gene FAM48A through cis-expression. Our results provide useful information on the mutation of LncFAM, which can be used as a potential molecular breeding marker.
Biological Parameters of Two Triatoma rubida Subspecies (Hemiptera: Reduviidae) and Their Laboratory Hybrids
Authors: Martínez-Ibarra José Alejandro , Nogueda-Torres Benjamín , Montañez-Valdez Oziel Dante , Michel-Parra J Guadalupe , Valenzuela-Campos Ricardo
Published: April 2020

Chagas disease is one of the most important vector-borne diseases in Latin America, including Mexico. Recently, autochthonous cases have also been detected in the United States of America. It is suspected that two subspecies of Triatoma rubida (Uhler), T. r. sonoriana (Usinger) and T. r. uhleri (Usinger), considered efficient vectors of Trypanosoma cruzi Chagas in Mexico, could interbreed and potentially generate offspring with superior biological characteristics. In this study, the biological parameters of T. r. sonoriana, T. r. uhleri and their laboratory hybrids were evaluated. Hybrids of the two subspecies surpassed both parental subspecies, T. r. sonoriana and T. r. uhleri, in three (numbers of required blood meals to molt [16–20], feeding [10.5–17 min] and defecation times [˂1 min post-feeding]) of nine studied biological parameters. Moreover, the hybrids surpassed T. r. uhleri in two additional parameters, development time (298 d) and mortality (39–42%). Both the hybrid and the two parental cohorts had comparable results in the remaining four (onset of feeding, number of obtained females, number of eggs laid, and eclosion rate) of nine studied parameters. Thus, we conclude that hybrid vigor could result in an increased risk of T. cruzi transmission to humans and animals.
Laboratory Studies of Questing Behavior in Colonized Nymphal Amblyomma maculatum Ticks (Acari: Ixodidae)
Authors: Portugal José Santos , Wills Robert , Goddard Jerome
Published: April 2020

Environmental factors affect host-seeking behavior in ticks. In this study, 80 nymphal Amblyomma maculatum Koch were released in an observation arena containing four different heights of broomsedge stems (Andropogon virginicus L.) anchored in sand. Observations were made over three days as to proportion of ticks questing, questing height, and stem height distribution This scenario was replicated three times with different cohorts of ticks (n = 80 per replicate) for each of three treatment combinations of temperature and humidity: High temperature/high humidity (HTHH), high temperature/low humidity (HTLH), and low temperature/high humidity (LTHH). A fourth treatment utilizing the same size cohort and number of replicates included Wind (HTHHW+/−) by alternating days of wind and no-wind conditions over four days. Mean questing height for ticks under HTHH, HTLH, and LTHH conditions ranged from 4.45 to 6.03 cm with ticks questing significantly higher in HTHH. A significantly lower proportion ticks quested in HTLH (8.64%) than HTHH (14.06%) and LTHH (15.33%). In HTHH and LTHH, a significantly higher proportion of ticks were observed questing on 5-cm stems. Wind significantly reduced average questing height, and when absent, ticks on 20- and 30-cm stems quested significantly higher. These data indicate that A. macuatum nymphs randomly select stems to quest upon and climb upward until environmental conditions are prohibitive/ideal. Conditions with reduced vapor pressure deficit (VPD) led to higher questing frequency and height. Relatively low questing heights observed correspond with size of preferred hosts and may explain infrequency of collection by dragcloth in the field.
Fine structure of Aldrovanda vesiculosa L: the peculiar lifestyle of an aquatic carnivorous plant elucidated by electron microscopy using cryo-techniques
Authors: Atsuzawa Kimie , Kanaizumi Daiki , Ajisaka Mizuki , Kamada Tasuku , Sakamoto Kimie , Matsushima Hisashi , Kaneko Yasuko
Published: April 2020

The aquatic carnivorous plant Aldrovanda vesiculosa L. is critically endangered worldwide; its peculiar lifestyle raises many questions and poses problems both intriguing on their own and relevant to conservation. While establishing a culture system for its propagation and restoring its natural habitat in Hozoji pond in Saitama, Japan, we conducted ultrastructural observations to examine the various aspects of Aldrovanda’s way of life. Electron microscopic observation in combination with cryo-techniques produced novel information which could not be obtained by other methods. Some of the results are: phosphorous is stored in petiole cells of turions during winter; mucilaginous guides are provided for pollen tubes in parietal placental ovaries; storage of potassium in the vicinity of the midrib of carnivorous leaves may contribute to the rapid closing of the carnivorous leaves; dynamic sequential changes of the ultrastructure of digestive glands are involved in the synthesis and secretion of digestive enzymes, including protease and acid phosphatase. These results should contribute significantly to our understanding of Aldrovanda and the detailed mechanisms of its life.
Do hepatic artery infusion pumps cause recurrent pleural effusions?
Authors: Harris Emily Ann , Castillon Rafael Garza , Bhakta Priya
Published: April 2020

Hepatic artery infusion pump chemotherapy (HAIPC) for colorectal liver metastasis (CRLM) is a new technique in the treatment of CRLM, whose side effects are not well studied. Case Report: This paper aims to understand the side effect profile of HAIPC as it relates to recurrent pleural effusions. This is a case report of a 48-year-old male with CRLM being treated with HAIPC, who presents with recurrent pleural effusions found to be benign/transudative after right-side video-assisted thoracoscopic surgery. Discussion: This study suggests that HAIPC causes recurrent sympathetic pleural effusions as a side effect of the perihepatic inflammation of the localized chemotherapy treatment. Furthermore, we question if sympathetic pleural effusions are a prelude to hepatic toxicity from HAIPC. Lastly, this paper aims to guide the differential diagnosis of pleural effusions in the cancer patient being treated with HAIPC.
Pulmonary embolism in a returning traveller with COVID-19 pneumonia
Authors: Foch Emilie , Allou Nathalie , Vitry Thierry , Masse Laurie , Allyn Jérôme , Andre Michel , Allou Nicolas
Published: April 2020

Pulmonary embolism and COVID-19 pneumonia
Large-scale structures in the ΛCDM Universe: network analysis and machine learning
Authors: Tsizh Maksym , Novosyadlyj Bohdan , Holovatch Yurij , Libeskind Noam I
Published: April 2020

We perform an analysis of the cosmic web as a complex network, which is built on a Λ cold dark matter (ΛCDM) cosmological simulation. For each of nodes, which are in this case dark matter haloes formed in the simulation, we compute 10 network metrics, which characterize the role and position of a node in the network. The relation of these metrics to topological affiliation of the halo, i.e. to the type of large-scale structure, which it belongs to, is then investigated. In particular, the correlation coefficients between network metrics and topology classes are computed. We have applied different machine learning methods to test the predictive power of obtained network metrics and to check if one could use network analysis as a tool for establishing topology of the large-scale structure of the Universe. Results of such predictions, combined in the confusion matrix, show that it is not possible to give a good prediction of the topology of cosmic web (score is ≈70 ${{\rm per\ cent}}$ in average) based only on coordinates and velocities of nodes (haloes), yet network metrics can give a hint about the topological landscape of matter distribution.
EX draconis: using eclipses to separate outside-in and inside-out outbursts
Authors: Court J M C , Scaringi S , Littlefield C , Castro Segura N , Long K S , Maccarone T , Altamirano D , Degenaar N , Wijnands R , Shahbaz T , Zhan Z
Published: April 2020

We present a study of the eclipses in the accreting white dwarf EX draconis (EX Dra) during TESS Cycles 14 and 15. During both of the two outbursts present in this data set, the eclipses undergo a hysteretic loop in eclipse-depth/out-of-eclipse-flux space. In each case, the direction in which the loops are executed strongly suggests an outburst that is triggered near the inner edge of the accretion disc and propagates outwards. This in turn suggests that the outbursts in EX Dra are ‘inside out’ outbursts; events predicted by previous hydrodynamic studies of dwarf nova accretion discs and confirmed spectroscopically in a number of other accreting white dwarf systems. We therefore propose that the direction of the loop executed in eclipse-depth/out-of-eclipse flux space be used as a test to phenomenologically distinguish between ‘inside out’ and ‘outside in’ outbursts in other eclipsing dwarf novae; a reliable and purely photometric test to differentiate between these phenomena.
On the ejection of dark matter from globular clusters
Authors: Hurst Travis J , Zentner Andrew R
Published: April 2020

We investigate analytically whether in a close encounter with a star, a dark matter (DM) particle can be accelerated above the escape speed of a globular cluster and be ejected. We find that this mechanism is not sufficient to eject a massive, extended DM halo by this time. Combined with observations of isolated globular clusters that may not have had their haloes tidally stripped, these results cast doubt on the scenario in which globular clusters formed in DM haloes.
Ion irradiation of acetylene ice in the ISM and the outer Solar system: laboratory simulations
Authors: Pereira R C , de Barros A L F , da Costa C A P , Oliveira P R B , Fulvio D , da Silveira E F
Published: April 2020

ABSTRACT)3

Acetylene, C2H2, has been observed in the interstellar medium, mostly around young stellar objects, as well as in molecular clouds and cometary comae, representing an important species of astrophysical interest. In this work, we present a laboratory study of the C2H2 radiolysis at 45 K for three different beams and energies: 1.0 MeV H+ and He+, and 1.0 and 1.5 MeV N+ beams. Fourier transform infrared spectroscopy was used for monitoring the molecular changes induced by the ion processing. Two different sample thicknesses were irradiated; for the thicker one, implantation had occurred. Spectra and absorbance evolutions for the thin and thick films are qualitatively different. Four C2H2 bands are observed at 3225, 1954, 1392, and 763 cm−1. The C2H2 compaction and apparent destruction cross-sections are determined. For the case of the H+ beam, the compaction cross-section dominates. Concerning molecular synthesis by irradiation, New product bands were not observed in the thin ice irradiations; for the thicker film ice, the daughter species CH4, C2H4, C3H6, and C4H4 have been identified and their destruction and formation cross-sections determined. The apparent destruction cross-section was found to be a function of the electronic stopping power (Se) as σd ∝ S$_\mathrm{ e}^{3/2}$. The half-life of the C2H2 bombarded by galactic cosmic rays is estimated. The current findings are a contribution to the understanding of how the molecules synthesized upon irradiation of Interstellar and outer Solar system ices participate to the molecular enrichment and to the physicochemical evolution of the Universe.
A new and simple prescription for planet orbital migration and eccentricity damping by planet–disc interactions based on dynamical friction
Authors: Ida Shigeru , Muto Takayuki , Matsumura Soko , Brasser Ramon
Published: April 2020

During planet formation, gravitational interaction between a planetary embryo and the protoplanetary gas disc causes orbital migration of the planetary embryo, which plays an important role in shaping the final planetary system. While migration sometimes occurs in the supersonic regime, wherein the relative velocity between the planetary embryo and the gas is higher than the sound speed, migration prescriptions proposed thus far describing the planet–disc interaction force and the time-scales of orbital change in the supersonic regime are inconsistent with one another. Here we discuss the details of existing prescriptions in the literature and derive a new simple and intuitive formulation for planet–disc interactions based on dynamical friction, which can be applied in both supersonic and subsonic cases. While the existing prescriptions assume particular disc models, ours include the explicit dependence on the disc parameters; hence, it can be applied to discs with any radial surface density and temperature dependence (except for the local variations with radial scales less than the disc scale height). Our prescription will reduce the uncertainty originating from different literature formulations of planet migration and will be an important tool to study planet accretion processes, especially when studying the formation of close-in low-mass planets that are commonly found in exoplanetary systems.
Imprints of the redshift evolution of double neutron star merger rate on the signal-to-noise ratio distribution
Authors: Kastha Shilpa , Saleem M , Arun K G
Published: April 2020

Proposed third-generation gravitational wave interferometers such as Cosmic Explorer (CE) will have the sensitivity to observe double neutron star mergers (DNS) up to a redshift of ∼5 with good signal-to-noise ratios (SNRs). We argue that the comoving spatial distribution of DNS mergers leaves a unique imprint on the statistical distribution of SNRs of the detected DNS mergers. Hence, the SNR distribution of DNS mergers will facilitate a novel probe of their redshift evolution independent of the luminosity distance measurements. We consider detections of DNS mergers by the CE and study the SNR distribution for different possible redshift evolution models of DNSs and employ Anderson Darling p-value statistic to demonstrate the distinguishability between these different models. We find that a few hundreds of DNS mergers in the CE era will allow us to distinguish between different models of redshift evolution. We further apply the method for various SNR distributions arising due to different merger delay-time and star formation rate (SFR) models and show that for a given SFR model, the SNR distributions are sensitive to the delay-time distributions. Finally, we investigate the effects of sub-threshold events in distinguishing between different merger rate distribution models.
Omega Centauri: weak MgH band in red giants directly traces the helium content
Authors: Reddy Arumalla B S
Published: April 2020

High spectral resolution and high signal-to-noise ratio optical spectra of red giants in the globular cluster Omega Centauri are analysed for stellar parameters and chemical abundances of 15 elements including helium by either line equivalent widths or synthetic spectrum analyses. The simultaneous abundance analysis of MgH and Mg lines adopting theoretical photospheres and a combination of He/H ratios proved to be the only powerful probe to evaluate helium abundances of red giants cooler than 4400 K, wherein otherwise helium line transitions (He i 10830 and 5876 Å) present for a direct spectral line analysis. The impact of helium-enhanced model photospheres on the resulting abundance ratios is smaller than 0.15 dex, in agreement with past studies. The first indirect spectroscopic helium abundances measured in this paper for the most metal-rich cluster members reveal the discovery of seven He-enhanced giants ($\Delta Y=+0.15 \pm 0.04$), the largest such sample found spectroscopically to date. The average metallicity of −0.79 ± 0.06 dex and abundances for O, Na, Al, Si, Ca, Ti, Ni, Ba, and La are consistent with values found for the red giant branch (RGB-a) and subgiant branch (SGB-a) populations of Omega Centauri, suggesting an evolutionary connection among samples. The He enhancement in giants is associated with larger s-process elemental abundances, which correlate with Al and anticorrelate with O. These results support the formation of He-enhanced, metal-rich population of Omega Centauri out of the interstellar medium enriched with the ejecta of fast rotating massive stars, binaries exploding as supernovae, and asymptotic giant branch (AGB) stars.
Mapping and characterization of cosmic filaments in galaxy cluster outskirts: strategies and forecasts for observations from simulations
Authors: Kuchner Ulrike , Aragón-Salamanca Alfonso , Pearce Frazer R , Gray Meghan E , Rost Agustín , Mu Chunliang , Welker Charlotte , Cui Weiguang , Haggar Roan , Laigle Clotilde , Knebe Alexander , Kraljic Katarina , Sarron Florian , Yepes Gustavo
Published: April 2020

Upcoming wide-field surveys are well suited to studying the growth of galaxy clusters by tracing galaxy and gas accretion along cosmic filaments. We use hydrodynamic simulations of volumes surrounding 324 clusters from The ThreeHundred project to develop a framework for identifying and characterizing these filamentary structures and associating galaxies with them. We define three-dimensional reference filament networks reaching 5R200 based on the underlying gas distribution and quantify their recovery using mock galaxy samples mimicking observations such as those of the WEAVE Wide-Field Cluster Survey. Since massive galaxies trace filaments, they are best recovered by mass-weighting galaxies or imposing a bright limit (e.g. >L*) on their selection. We measure the transverse gas density profile of filaments, derive a characteristic filament radius of ≃ 0.7–1 h−1Mpc, and use this to assign galaxies to filaments. For different filament extraction methods, we find that at R > R200, ∼15–$20{{\ \rm per\ cent}}$ of galaxies with M* > 3 × 109M⊙ are in filaments, increasing to $\sim 60{{\ \rm per\ cent}}$ for galaxies more massive than the Milky Way. The fraction of galaxies in filaments is independent of cluster mass and dynamical state and is a function of cluster-centric distance, increasing from ∼13 per cent at 5R200 to ∼21 per cent at 1.5R200. As a bridge to the design of observational studies, we measure the purity and completeness of different filament galaxy selection strategies. Encouragingly, the overall three-dimensional filament networks and ∼67 per cent of the galaxies associated with them are recovered from two-dimensional galaxy positions.
The hydrogen Balmer lines and jump in absorption in accretion disc modelling – an ultraviolet–optical spectral analysis of the dwarf novae UZ Serpentis and CY Lyrae
Authors: Godon Patrick , Sion Edward M , Szkody Paula , Blair William P
Published: April 2020

The spectra of disc-dominated cataclysmic variables (CVs) often deviate from the spectra of accretion disc models; in particular, the Balmer jump and absorption lines are found to be shallower in the observations than in the models. We carried out a combined ultraviolet–optical spectral analysis of two dwarf novae (DNe): UZ Ser in outburst, decline, and quiescence, and CY Lyr on the rise to outburst and in outburst. We fit the Balmer jump and absorption lines, the continuum flux level and slope by adjusting the accretion rate, inclination, and disc outer radius. For both systems, we find an accretion rate $\dot{M} \approx 8 \times 10^{-9}\,\mathrm{ M}_\odot\,\mathrm{ yr}^{-1}$ in outburst, and $\dot{M} \approx 2-3 \times 10^{-9}\,\mathrm{ M}_\odot\,\mathrm{ yr}^{-1}$ for the rise and decline phases. The outer disc radius we derive is smaller than expected (Rdisc ≈ 0.2a, where a is the binary separation), except during late rise (for CY Lyr) where Rdisc = 0.3a. UZ Ser also reveals a 60 000 K white dwarf. These results show that during a DN cycle the radius of the disc is the largest just before the peak of the outburst, in qualitative agreement with the disc instability model for DN outbursts. We suspect that an additional emitting component (e.g. disc wind) is also at work to reduce the slope of the continuum and size of the Balmer jump and absorption lines. We stress that both the outer disc radius and disc wind need to be taken into account for more realistic disc modelling of CVs.
LIST-S2: taxonomy based sorting of deleterious missense mutations across species
Authors: Malhis Nawar , Jacobson Matthew , Jones Steven J M , Gsponer Jörg
Published: April 2020

The separation of deleterious from benign mutations remains a key challenge in the interpretation of genomic data. Computational methods used to sort mutations based on their potential deleteriousness rely largely on conservation measures derived from sequence alignments. Here, we introduce LIST-S2, a successor to our previously developed approach LIST, which aims to exploit local sequence identity and taxonomy distances in quantifying the conservation of human protein sequences. Unlike its predecessor, LIST-S2 is not limited to human sequences but can assess conservation and make predictions for sequences from any organism. Moreover, we provide a web-tool and downloadable software to compute and visualize the deleteriousness of mutations in user-provided sequences. This web-tool contains an HTML interface and a RESTful API to submit and manage sequences as well as a browsable set of precomputed predictions for a large number of UniProtKB protein sequences of common taxa. LIST-S2 is available at: https://list-s2.msl.ubc.ca/
The geometric influence on the Cys2His2 zinc finger domain and functional plasticity
Authors: Mueller April L , Corbi-Verge Carles , Giganti David O , Ichikawa David M , Spencer Jeffrey M , MacRae Mark , Garton Michael , Kim Philip M , Noyes Marcus B
Published: April 2020

The Cys2His2 zinc finger is the most common DNA-binding domain expanding in metazoans since the fungi human split. A proposed catalyst for this expansion is an arms race to silence transposable elements yet it remains poorly understood how this domain is able to evolve the required specificities. Likewise, models of its DNA binding specificity remain error prone due to a lack of understanding of how adjacent fingers influence each other's binding specificity. Here, we use a synthetic approach to exhaustively investigate binding geometry, one of the dominant influences on adjacent finger function. By screening over 28 billion protein–DNA interactions in various geometric contexts we find the plasticity of the most common natural geometry enables more functional amino acid combinations across all targets. Further, residues that define this geometry are enriched in genomes where zinc fingers are prevalent and specificity transitions would be limited in alternative geometries. Finally, these results demonstrate an exhaustive synthetic screen can produce an accurate model of domain function while providing mechanistic insight that may have assisted in the domains expansion.
Evolutionary selection of pestivirus variants with altered or no microRNA dependency
Authors: Kokkonos Konstantinos G , Fossat Nicolas , Nielsen Louise , Holm Christina , Hepkema Wytske M , Bukh Jens , Scheel Troels K H
Published: April 2020

Host microRNA (miRNA) dependency is a hallmark of the human pathogen hepatitis C virus (HCV) and was also described for the related pestiviruses, which are important livestock pathogens. The liver-specific miR-122 binds within the HCV 5′ untranslated region (UTR), whereas the broadly expressed let-7 and miR-17 families bind two sites (S1 and S2, respectively) in the pestiviral 3′ UTR. Here, we dissected the mechanism of miRNA dependency of the pestivirus bovine viral diarrhea virus (BVDV). Argonaute 2 (AGO2) and miR-17 binding were essential for viral replication, whereas let-7 binding was mainly required for full translational efficiency. Furthermore, using seed site randomized genomes and evolutionary selection experiments, we found that tropism could be redirected to different miRNAs. AGO cross-linking and immunoprecipitation (CLIP) experiments and miRNA antagonism demonstrated that these alternative variants bound and depended on the corresponding miRNAs. Interestingly, we also identified miRNA-independent variants that were obtained through acquisition of compensatory mutations near the genomic 3′ terminus. Rescue experiments demonstrated that miRNA binding and 3′ mutagenesis contribute to replication through mutually exclusive mechanisms. Altogether, our findings suggest that pestiviruses, although capable of miRNA-independent replication, took advantage of miRNAs as essential host factors, suggesting a favorable path during evolutionary adaptation.
Structural insight into DNA joining: from conserved mechanisms to diverse scaffolds
Authors: Williamson Adele , Leiros Hanna-Kirsti S
Published: April 2020

DNA ligases are diverse enzymes with essential functions in replication and repair of DNA; here we review recent advances in their structure and distribution and discuss how this contributes to understanding their biological roles and technological potential. Recent high-resolution crystal structures of DNA ligases from different organisms, including DNA-bound states and reaction intermediates, have provided considerable insight into their enzymatic mechanism and substrate interactions. All cellular organisms possess at least one DNA ligase, but many species encode multiple forms some of which are modular multifunctional enzymes. New experimental evidence for participation of DNA ligases in pathways with additional DNA modifying enzymes is defining their participation in non-redundant repair processes enabling elucidation of their biological functions. Coupled with identification of a wealth of DNA ligase sequences through genomic data, our increased appreciation of the structural diversity and phylogenetic distribution of DNA ligases has the potential to uncover new biotechnological tools and provide new treatment options for bacterial pathogens.
The Quest for Orthologs benchmark service and consensus calls in 2020
Authors: Altenhoff Adrian M , Garrayo-Ventas Javier , Cosentino Salvatore , Emms David , Glover Natasha M , Hernández-Plaza Ana , Nevers Yannis , Sundesha Vicky , Szklarczyk Damian , Fernández José M , Codó Laia , for Orthologs Consortium the Quest , Gelpi Josep Ll , Huerta-Cepas Jaime , Iwasaki Wataru , Kelly Steven , Lecompte Odile , Muffato Matthieu , Martin Maria J , Capella-Gutierrez Salvador , Thomas Paul D , Sonnhammer Erik , Dessimoz Christophe
Published: April 2020

The identification of orthologs—genes in different species which descended from the same gene in their last common ancestor—is a prerequisite for many analyses in comparative genomics and molecular evolution. Numerous algorithms and resources have been conceived to address this problem, but benchmarking and interpreting them is fraught with difficulties (need to compare them on a common input dataset, absence of ground truth, computational cost of calling orthologs). To address this, the Quest for Orthologs consortium maintains a reference set of proteomes and provides a web server for continuous orthology benchmarking (http://orthology.benchmarkservice.org). Furthermore, consensus ortholog calls derived from public benchmark submissions are provided on the Alliance of Genome Resources website, the joint portal of NIH-funded model organism databases.
BREM-SC: a bayesian random effects mixture model for joint clustering single cell multi-omics data
Authors: Wang Xinjun , Sun Zhe , Zhang Yanfu , Xu Zhongli , Xin Hongyi , Huang Heng , Duerr Richard H , Chen Kong , Ding Ying , Chen Wei
Published: April 2020

Droplet-based single cell transcriptome sequencing (scRNA-seq) technology, largely represented by the 10× Genomics Chromium system, is able to measure the gene expression from tens of thousands of single cells simultaneously. More recently, coupled with the cutting-edge Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq), the droplet-based system has allowed for immunophenotyping of single cells based on cell surface expression of specific proteins together with simultaneous transcriptome profiling in the same cell. Despite the rapid advances in technologies, novel statistical methods and computational tools for analyzing multi-modal CITE-Seq data are lacking. In this study, we developed BREM-SC, a novel Bayesian Random Effects Mixture model that jointly clusters paired single cell transcriptomic and proteomic data. Through simulation studies and analysis of public and in-house real data sets, we successfully demonstrated the validity and advantages of this method in fully utilizing both types of data to accurately identify cell clusters. In addition, as a probabilistic model-based approach, BREM-SC is able to quantify the clustering uncertainty for each single cell. This new method will greatly facilitate researchers to jointly study transcriptome and surface proteins at the single cell level to make new biological discoveries, particularly in the area of immunology.
The ancillary N-terminal region of the yeast AP-1 transcription factor Yap8 contributes to its DNA binding specificity
Authors: Maciaszczyk-Dziubinska Ewa , Reymer Anna , Kumar Nallani Vijay , Białek Wojciech , Mizio Katarzyna , Tamás Markus J , Wysocki Robert
Published: April 2020

Activator protein 1 (AP-1) is one of the largest families of basic leucine zipper (bZIP) transcription factors in eukaryotic cells. How AP-1 proteins achieve target DNA binding specificity remains elusive. In Saccharomyces cerevisiae, the AP-1-like protein (Yap) family comprises eight members (Yap1 to Yap8) that display distinct genomic target sites despite high sequence homology of their DNA binding bZIP domains. In contrast to the other members of the Yap family, which preferentially bind to short (7–8 bp) DNA motifs, Yap8 binds to an unusually long DNA motif (13 bp). It has been unclear what determines this unique specificity of Yap8. In this work, we use molecular and biochemical analyses combined with computer-based structural design and molecular dynamics simulations of Yap8–DNA interactions to better understand the structural basis of DNA binding specificity determinants. We identify specific residues in the N-terminal tail preceding the basic region, which define stable association of Yap8 with its target promoter. We propose that the N-terminal tail directly interacts with DNA and stabilizes Yap8 binding to the 13 bp motif. Thus, beside the core basic region, the adjacent N-terminal region contributes to alternative DNA binding selectivity within the AP-1 family.