bluuebunny/crossref_metadata_2025 huggingface dataset:
Subcellular Propagation of Cardiomyocyte β-Adrenergic Activation of Calcium Uptake Involves Internal β-Receptors and AKAP7
Authors: Shannon Thomas R , Bare Dan J , Van Dijk Sabine , Raofi Shayan , Huynh Tiffany N-M , Xiang Yang K , Bossuyt Julie , Dodge-Kafka Kimberly L , Ginsburg Kenneth S , Bers Donald M
Published: May 2022

β-adrenergic receptor (β-AR) signaling in cardiac myocytes is central to cardiac function, but spatiotemporal activation within myocytes is unresolved. In rabbit ventricular myocytes, β-AR agonists or high extracellular [Ca] were applied locally at one end, to measure β-AR signal propagation as Ca−transient (CaT) amplitude and sarcoplasmic reticulum (SR) Ca uptake. High local [Ca]o, increased CaT amplitude under the pipette faster than did ISO, but was also more spatially restricted. Local isoproterenol (ISO) or norepinephrine (NE) increased CaT amplitude and SR Ca uptake, that spread along the myocyte to the unexposed end. Thus, local [Ca]i decline kinetics reflect spatio-temporal progression of β-AR end-effects in myocytes. To test whether intracellular β-ARs contribute to this response, we used β-AR-blockers that are membrane permeant (propranolol) or not (sotalol). Propranolol completely blocked NE-dependent CaT effects. However, blocking surface β-ARs only (sotalol) suppressed only ∼50% of the NE-induced increase in CaT peak and rate of [Ca]i decline, but these changes spread more gradually than NE alone. We also tested whether A-kinase anchoring protein 7γ (AKAP7γ; that interacts with phospholamban) is mobile, such that it might contribute to intracellular spatial propagation of β-AR signaling. We found AKAP7γ to be highly mobile using fluorescence recovery after photobleach of GFP tagged AKAP7γ, and that PKA activation accelerated AKAP7γ-GFP wash-out upon myocyte saponin-permeabilization, suggesting increased AKAP7γ mobility. We conclude that local β-AR activation can activate SR Ca uptake at remote myocyte sites, and that intracellular β-AR and AKAP7γ mobility may play a role in this spread of activation.
Disclosing azole resistance mechanisms in resistant Candida glabrata strains encoding wild-type or gain-of-function CgPDR1 alleles through comparative genomics and transcriptomics
Authors: Salazar Sara B , Pinheiro Maria Joana F , Sotti-Novais Danielle , Soares Ana R , Lopes Maria M , Ferreira Teresa , Rodrigues Vitória , Fernandes Fábio , Mira Nuno P
Published: May 2022

The pathogenic yeast Candida glabrata is intrinsically resilient to azoles and rapidly acquires resistance to these antifungals, in vitro and in vivo. In most cases azole-resistant C. glabrata clinical strains encode hyperactive CgPdr1 variants, however, resistant strains encoding wild-type CgPDR1 alleles have also been isolated, although remaining to be disclosed the underlying resistance mechanism. In this study, we scrutinized the mechanisms underlying resistance to azoles of 8 resistant clinical C. glabrata strains, identified along the course of epidemiological surveys undertaken in Portugal. Seven of the strains were found to encode CgPdr1 gain-of-function variants (I392M, E555K, G558C, and I803T) with the substitutions I392M and I803T being herein characterized as hyper-activating mutations for the first time. While cells expressing the wild-type CgPDR1 allele required the mediator subunit Gal11A to enhance tolerance to fluconazole, this was dispensable for cells expressing the I803T variant indicating that the CgPdr1 interactome is shaped by different gain-of-function substitutions. Genomic and transcriptomic profiling of the sole azole-resistant C. glabrata isolate encoding a wild-type CgPDR1 allele (ISTB218) revealed that under fluconazole stress this strain over-expresses various genes described to provide protection against this antifungal, while also showing reduced expression of genes described to increase sensitivity to these drugs. The overall role in driving the azole-resistance phenotype of the ISTB218 C. glabrata isolate played by these changes in the transcriptome and genome of the ISTB218 isolate are discussed shedding light into mechanisms of resistance that go beyond the CgPdr1-signalling pathway and that may alone, or in combination, pave the way for the acquisition of resistance to azoles in vivo.
Promoting Social Capital for Healthy Aging: Towards an Integrative Framework
Authors: Lu Shiyu , Chui Cheryl , Lum Terry
Published: May 2022

There is no theoretical framework to guide society to enhance social capital among older adults in the Decade of Healthy Aging. This article aims to advance scholarship by providing a theoretical framework for promoting social capital for healthy aging using timebanking as a case illustration. We provide an integrated theoretical framework to enhance social capital for healthy aging by incorporating 3 core elements: (a) facilitating emotional meaningfulness via social participation for older adults, (b) incorporating older adults as coproducers in community development, and (c) nurturing an inclusive and equitable society. We further demonstrate the utility of the integrated theoretical framework for gerontologists by conceptualizing timebanking as an intervention for enhancing social capital in an aging society.
Involution and symbiosis: the self-perpetuating conflict in the Democratic Republic of Congo
Authors: Stearns Jason
Published: May 2022

Literature on conflict duration emphasizes the importance of material factors, commitment problems and information asymmetries. Using the case study of the Democratic Republic of the Congo, and drawing on interviews with 138 sources involved in the conflict, this article advances a theory of conflict duration that highlights the role that interests, identities and the social anchorage of belligerents play. Together, they explain how the conflict in the Congo has become an end in itself for belligerents, carried forward by its own momentum. This article describes the key factors: a proliferation of actors, the rise of a military bourgeoisie, the involution of interests, and the symbiosis of belligerents. A similar argument can be applied to other protracted conflicts in large and weak states. This understanding of conflict has repercussions for policy, as it suggests that there is no inherent link between elite political settlements and stability. It pushes away from the technocratic approach to institution-building to centre the role of the state and political culture in debates over peacebuilding.
High Attack Rate of Severe Acute Respiratory Syndrome Coronavirus 2 B.1.1.529 Among 2-Dose Vaccinated Populations in 2 Indoor Entertainment Setting Outbreaks
Authors: Liu Bette , Stepien Sandrine , Pye Victoria , Law Charlee , Dalton Craig , Durrheim David N , Macartney Kristine
Published: May 2022

We estimated attack rates of severe acute respiratory syndrome coronavirus 2 Omicron (B.1.1.529) infection among people attending a nightclub and a graduation ball where >95% had at least 2 vaccine doses. Attack rates were 295 of 535 (55.1%) and 102 of 189 (54.0%), respectively (mean, 5 days postevent). At the ball, attack rates increased with time since vaccination: 12.5% among those vaccinated 1–2 months previously and 68.0% among those vaccinated ≥3 months previously; such differences were not found at the nightclub. Recent vaccination prevents Omicron infection, but is time and setting dependent, emphasizing the importance of nonpharmaceutical public health measures in addition to vaccine booster doses to maximize protection in high-risk contexts.
Lung-AdaptedStaphylococcus aureusIsolates With Dysfunctional Agr System Trigger a Proinflammatory Response
Authors: Ramond Elodie , Lepissier Agathe , Ding Xiongqi , Bouvier Clémence , Tan Xin , Euphrasie Daniel , Monbernard Pierre , Dupuis Marion , Saubaméa Bruno , Nemazanyy Ivan , Nassif Xavier , Ferroni Agnès , Sermet-Gaudelus Isabelle , Charbit Alain , Coureuil Mathieu , Jamet Anne
Published: May 2022

Background

Staphylococcus aureus dominates the lung microbiota of children with cystic fibrosis (CF) and persistent clones are able to establish chronic infection for years, having a direct deleterious impact on lung function. However, in this context, the exact contribution of S. aureus to the decline in respiratory function in children with CF is not elucidated.

Methods

To investigate the contribution of persistent S. aureus clones in CF disease, we undertook the analysis of sequential isogenic isolates recovered from 15 young CF patients.

Results

Using an air-liquid infection model, we observed a strong correlation between S. aureus adaption in the lung (late isolates), low toxicity, and proinflammatory cytokine secretion. Conversely, early isolates appeared to be highly cytotoxic but did not promote cytokine secretion. We found that cytokine secretion was dependent on staphylococcal protein A (Spa), which was selectively expressed in late compared to early isolates as a consequence of dysfunctional agr quorum-sensing system. Finally, we demonstrated the involvement of TNF-α receptor 1 signaling in the inflammatory response of airway epithelial cells to these lung-adapted S. aureus isolates.

Conclusions

Our results suggest an unexpected direct role of bacterial lung adaptation in the progression of chronic lung disease by promoting a proinflammatory response through acquired agr dysfunction.
Sixteen in One: White-Belted Megaselia Rondani (Diptera: Phoridae) From the New World Challenge Species Concepts
Authors: Brown Brian V , Hartop Emily A , Wong Maria A
Published: May 2022

We review the species of Megaselia similar to Megaselia sulphurizona Borgmeier. A close examination of M. sulphurizona indicates that its current concept includes at least 16 species, 15 of which— Megaselia albizona, Megaselia borealizona, Megaselia colombizona, Megaselia cryptizona, Megaselia danizona, Megaselia guanizona, Megaselia marizona, Megaselia nivizona, Megaselia oklizona, Megaselia paulizona, Megaselia reductizona, Megaselia solizona, Megaselia tropizona, Megaselia wendizona, and Megaselia winnizona are described as new, based primarily on molecular data. The identity of the holotype of the species M. sulphurizona is clarified through wing vein morphometrics. Two of the new species, M. albizona and M. cryptizona, are the 47th and 48th new species of phorid fly described from the BioSCAN project, an urban biodiversity study in Los Angeles, California, U.S.
Genomic-based transmission analysis of carbapenem-resistant Pseudomonas aeruginosa at a tertiary care centre in Cologne (Germany) from 2015 to 2020
Authors: Wendel Andreas F. , Malecki Monika , Mattner Frauke , Xanthopoulou Kyriaki , Wille Julia , Seifert Harald , Higgins Paul G.
Published: May 2022

Objectives

To describe the propensity of carbapenem-resistant Pseudomonas aeruginosa to spread within a hospital critical care setting.

Methods

The study was conducted in a 700-bed tertiary centre in Cologne, Germany. P. aeruginosa resistant to piperacillin, ceftazidime, cefepime, imipenem, meropenem and ciprofloxacin, isolated from clinical and screening specimens from four critical care units from 2015 to 2020 were analysed. Genotyping was carried out by WGS (Illumina and MinION). MLST, core genome MLST (cgMLST) and resistome analysis was performed and merged with epidemiological data.

Results

Fifty-five out of 79 non-duplicate P. aeruginosa isolates were available, of which 20 were carbapenemase producers as follows: blaVIM-1 (n = 1), blaVIM-2 (n = 17), blaVIM-4 (n = 1), and blaNDM-1/blaGES-5 (n = 1). Forty-two of 55 isolates were hospital-acquired. cgMLST revealed three clusters: Cluster 1 (n = 15, ST111, blaVIM-2, recovered between 2015 and 2020); Cluster 2 (n = 4, ST970, carbapenemase negative); and Cluster 3 (n = 2, ST357, carbapenemase negative). The blaVIM-2 gene of Cluster 1 was integrated on the chromosome in a class 1 integron (type In59). Using conventional epidemiology, we were only able to confirm two patient-to-patient transmissions and one room-to-patient transmission on three different ICUs within Cluster 1. Isolates from Cluster 2 represented an outbreak occurring in 2019.

Conclusions

These data give insight into the epidemiology of carbapenem-resistant P. aeruginosa. Transmission dynamics differed between carbapenemase- and non-carbapenemase-producing isolates. A continuous acquisition of clonally related ST111 VIM-2 P. aeruginosa, being the main carbapenemase-producing strain, was observed over the whole study period, as well as an overall higher genomic diversity among non-carbapenemase-producing P. aeruginosa.
Role of Breath Biopsy in COVID-19
Authors: Shekhawat Jyoti Kanwar , Banerjee Mithu
Published: May 2022

Background

COVID-19 is a highly contagious respiratory disease that can be transmitted through human exhaled breath. It has caused immense loss and has challenged the healthcare sector. It has affected the economy of countries and thereby affected numerous sectors. Analysis of human breath samples is an attractive strategy for rapid diagnosis of COVID-19 by monitoring breath biomarkers.

Content

Breath collection is a noninvasive process. Various technologies are employed for detection of breath biomarkers like mass spectrometry, biosensors, artificial learning, and machine learning. These tools have low turnaround time, robustness, and provide onsite results. Also, MS-based approaches are promising tools with high speed, specificity, sensitivity, reproducibility, and broader coverage, as well as its coupling with various chromatographic separation techniques providing better clinical and biochemical understanding of COVID-19 using breath samples.

Herein, we have tried to review the MS-based approaches as well as other techniques used for the analysis of breath samples for COVID-19 diagnosis. We have also highlighted the different breath analyzers being developed for COVID-19 detection.
The Human Rights Committee—Challenges and Prospects for Enhanced Effectiveness and Integration: A Comment
Authors: Kadelbach Stefan
Published: May 2022

The comment takes up the discussion by Ivana Jelić and Linus Mührel on the merits and deficits of the UN Human Rights Committee and the options for its reform. It advocates a view that takes contradictions between different perspectives on human rights into account, be they rooted in legal culture or in societal forces. It addresses discourse as the source of legitimacy and normativity of human rights, and therefore agrees with proposals to strengthen the treaty bodies within the framework of existing treaties, but also recalls the conditions of legal and societal discourse on the domestic plane.
Prevalence of sarcopenia in patients with gynecological cancer
Authors: Yamada Ryutaro , Todo Yukiharu , Minowa Kaoru , Minobe Shinichiro , Suzuki Yutaro , Kato Hidenori , Kurosu Hiroyuki , Mori Yoichi , Osanai Toshihisa
Published: May 2022

Background

The aim of the study was to investigate a prevalence of sarcopenia in patients with gynecological cancer in accordance with current diagnostic criteria of sarcopenia.

Methods

A series of 513 patients with gynecological cancer who were intended to newly receive initial or salvage treatment were recruited in a prospective study. Eligible patients were examined with dual energy X-ray absorptiometry and underwent handgrip strength test and the Short Physical Performance Battery before treatment. Sarcopenia was defined as both low skeletal muscle mass (skeletal muscle mass index) and low muscle strength (handgrip strength of <18.0 kg) or both low skeletal muscle mass index and low physical performance (Short Physical Performance Battery score of ≤9).

Results

A total of 475 patients (92.6%) were completely assessed in this study. Eligible patients’ median age was 60 years (range: 29–89 years). Frequencies of patients with low skeletal muscle mass index, low hand grip strength and low Short Physical Performance Battery were 118 (24.8%), 70 (14.7%) and 80 (16.8%), respectively. Sarcopenia was finally identified in 45 patients (9.5%), which accounted for 38.1% of patients with low skeletal muscle mass index, 64.3% of the patients with low hand grip strength and 56.3% of the patients with low physical performance, respectively.

Conclusions

The prevalence of sarcopenia of 9.5% in patients with gynecological malignancy who were scheduled to newly receive an initial or a salvage treatment. A large-scale, nation-wide study might be planned to elucidate an accurate prevalence of sarcopenia among gynecologic cancer patients.
Ecology and responses to climate change of biocrust-forming mosses in drylands
Authors: Ladrón de Guevara Mónica , Maestre Fernando T
Published: May 2022

Interest in understanding the role of biocrusts as ecosystem engineers in drylands has substantially increased during the past two decades. Mosses are a major component of biocrusts and dominate their late successional stages. In general, their impacts on most ecosystem functions are greater than those of early-stage biocrust constituents. However, it is common to find contradictory results regarding how moss interactions with different biotic and abiotic factors affect ecosystem processes. This review aims to (i) describe the adaptations and environmental constraints of biocrust-forming mosses in drylands, (ii) identify their primary ecological roles in these ecosystems, and (iii) synthesize their responses to climate change. We emphasize the importance of interactions between specific functional traits of mosses (e.g. height, radiation reflectance, morphology, and shoot densities) and both the environment (e.g. climate, topography, and soil properties) and other organisms to understand their ecological roles and responses to climate change. We also highlight key areas that should be researched in the future to fill essential gaps in our understanding of the ecology and the responses to ongoing climate change of biocrust-forming mosses. These include a better understanding of intra- and interspecific interactions and mechanisms driving mosses’ carbon balance during desiccation–rehydration cycles.
Ethylene Insensitive 3-Like 2 is a Brassicaceae-specific transcriptional regulator involved in fine-tuning ethylene responses in Arabidopsis thaliana
Authors: Houben Maarten , Vaughan-Hirsch John , Mou Wangshu , Van de Poel Bram
Published: May 2022

Ethylene signaling directs a pleiotropy of developmental processes in plants. In Arabidopsis, ethylene signaling converges at the master transcription factor Ethylene Insensitive 3 (EIN3), which has five homologs, EIN3-like 1–5 (EIL1–EIL5). EIL1 is most fully characterized and operates similarly to EIN3, while EIL3–5 are not involved in ethylene signaling. EIL2 remains less investigated. Our phylogenetic analysis revealed that EIL2 homologs have only been retrieved in the Brassicaceae family, suggesting that EIL2 diverged to have specific functions in the mustard family. By characterizing eil2 mutants, we found that EIL2 is involved in regulating ethylene-specific developmental processes in Arabidopsis thaliana, albeit in a more subtle way compared with EIN3/EIL1. EIL2 steers ethylene-triggered hypocotyl elongation in light-grown seedlings and is involved in lateral root formation. Furthermore, EIL2 takes part in regulating flowering time as eil2 mutants flower on average 1 d earlier and have fewer leaves. A pEIL2:EIL2:GFP translational reporter line revealed that EIL2 protein abundance is restricted to the stele of young developing roots. EIL2 expression, and not EIL2 protein stability, is regulated by ethylene in an EIN3/EIL1-dependent way. Despite EIL2 taking part in several developmental processes, the precise upstream and downstream regulation of this ethylene- and Brassicaceae-specific transcription factor remains to be elucidated.
Cytokinin oxidase/dehydrogenase inhibitors: outlook for selectivity and high efficiency
Authors: Nisler Jaroslav , Pěkná Zuzana , Končitíková Radka , Klimeš Pavel , Kadlecová Alena , Murvanidze Nino , Werbrouck Stefaan P O , Plačková Lenka , Kopečný David , Zalabák David , Spíchal Lukáš , Strnad Miroslav
Published: May 2022

Inhibitors of cytokinin oxidase/dehydrogenase (CKX) reduce the degradation of cytokinins in plants, and this effect can be exploited in agriculture and in plant tissue culture. In this study, we examine the structure–activity relationship of two series of CKX inhibitors based on diphenylurea. The compounds of Series I were derived from the recently published CKX inhibitors 3TFM-2HM and 3TFM-2HE, and we identified key substituents with increased selectivity for maize ZmCKX1 and ZmCKX4a over AtCKX2 from Arabidopsis. Series II contained compounds that further exceled in CKX inhibitory activity as well as in the ease of their synthesis. The best inhibitors exhibited half-maximal inhibitory concentration (IC50) values in low nanomolar ranges with ZmCKX1 and especially with ZmCKX4a, which is generally more resistant to inhibition. The activity of the key compounds was verified in tobacco and lobelia leaf-disk assays, where N6-isopentenyladenine was protected from degradation and promoted shoot regeneration. All the prepared compounds were further tested for toxicity against Caenorhabditis elegans, and the assays revealed clear differences in toxicity between compounds with and without a hydroxyalkyl group. In a broader perspective, this work increases our understanding of CKX inhibition and provides a more extensive portfolio of compounds suitable for agricultural and biotechnological research.
A dual-function transcription factor, SlJAF13, promotes anthocyanin biosynthesis in tomato
Authors: Chen Yunzhu , Kim Pyol , Kong Lingzhe , Wang Xin , Tan Wei , Liu Xin , Chen Yuansen , Yang Jianfei , Chen Bowei , Song Yuxin , An Zeyu , Min Phyon Jong , Zhang Yang , Ding Bing , Kawabata Saneyuki , Li Yuhua , Wang Yu
Published: May 2022

Unlike modern tomato (Solanum lycopersicum) cultivars, cv. LA1996 harbors the dominant Aft allele, which is associated with anthocyanin synthesis in tomato fruit peel. However, the control of Aft anthocyanin biosynthesis remains unclear. Here, we used ethyl methanesulfonate-induced and CRISPR/Cas9-mediated mutation of LA1996 to show, respectively, that two class IIIf basic helix–loop–helix (bHLH) transcription factors, SlJAF13 and SlAN1, are involved in the control of anthocyanin synthesis. These transcription factors are key components of the MYB–bHLH–WD40 (MBW) complex, which positively regulates anthocyanin synthesis. Molecular and genetic analyses showed that SlJAF13 functions as an upstream activation factor of SlAN1 by binding directly to the G-Box motif of its promoter region. On the other hand, SlJAZ2, a JA signaling repressor, interferes with formation of the MBW complex to suppress anthocyanin synthesis by directly binding these two bHLH components. Unexpectedly, the transcript level of SlJAZ2 was in turn repressed in a SlJAF13-dependent manner. Mechanistically, SlJAF13 interacts with SlMYC2, inhibiting SlMYC2 activation of SlJAZ2 transcription, thus constituting a negative feedback loop governing anthocyanin accumulation. Taken together, our findings support a sophisticated regulatory network, in which SlJAF13 acts as an upstream dual-function regulator that fine tunes anthocyanin biosynthesis in tomato.
An investigation of the magnetic activity of HD 134319 based on TESS photometry and ground-based spectroscopy
Authors: Xu Fukun , Gu Shenghong , Ioannidis Panogiotis
Published: May 2022

We present an analysis of the starspot properties and chromospheric activity on HD 134319 using high-precision photometry by Transiting Exoplanet Survey Satellite (TESS) in sectors 14–16 (T1) and 21–23 (T2) and high-resolution spectroscopy by the ELODIE spectrograph on 1.93-m telescope of Observatoire de Haute-Provence (OHP/ELODIE) and the High Resolution Echelle Spectrometer on Keck 10-m telescope of W. M. Keck Observatory (Keck/HIRES) during the years 1995–2013. We applied a two-spot model with generalized Lomb–Scargle (GLS) periodogram determined period of P = 4.436391 ± 0.00137 d to model chunks sliding over TESS light curve. We also measured the relative equivalent widths of Ca ii H and K, Hβ and Hα emissions by subtracting the overall spectrum from individual spectra. It was found that a two-spot configuration, namely a primary, slowly evolving and long-lasting spot (P) plus a secondary, rapidly evolving spot (S), was capable of explaining the data, although the actual starspot distribution cannot be derived from the collected data. Despite the spot radius–latitude degeneracy revealed in the best-fitting solutions, a sudden alternation between P and S radii followed by a gradual decrease of S in T1 and a decrease of both P and S from T1 to T2 were significant, corresponding to the evolution of magnetic activity. In addition, S revealed rotation and an oscillatory longitude migration synchronized to P in T1, but had a much larger migration than P in T2. This might indicate the evolution of the internal magnetic configuration. Chromospheric activity indicators were found to be tightly correlated with each other and revealed rotational modulation as well as a long-term decrease of emissions, implying the existence and evolution of magnetic activity on HD 134319.
The optical depth of foregrounds for the highest redshift 21 cm signals
Authors: Seitova Daniya , Pober Jonathan
Published: May 2022

Foreground emission makes it difficult to detect the highly redshifted cosmological 21 cm signal at any frequency. However, at low frequencies, foregrounds are likely to become optically thick, which would make it completely impossible to see a 21 cm signal behind them. To find out which regions of the sky might be optically thick for the highest redshifts of the 21 cm signal, we fit the measurements from LWA1 and the Haslam 408 MHz map with a two-component spectral model and calculate the frequency-dependent foreground optical depth point-by-point across the sky. Limitations of the current data prevent us from making any strong conclusions at high statistical significance, but there is suggestive evidence (∼1σ) that as much as 25 per cent of the sky could be obscured for the highest redshift 21 cm signals.
Cosmic void baryon acoustic oscillation measurement: Evaluation of sensitivity to selection effects
Authors: Forero-Sánchez Daniel , Zhao Cheng , Tao Charling , Chuang Chia-Hsun , Kitaura Francisco-Shu , Variu Andrei , Tamone Amélie , Kneib Jean-Paul
Published: May 2022

Cosmic voids defined as a subset of Delaunay Triangulation (DT) circumspheres have been used to measure the Baryon Acoustic Oscillations (BAO) scale; providing tighter constraints on cosmological parameters when combined with matter tracers. These voids are defined as spheres larger than a given radius threshold, which is constant over the survey volume. However, the response of these void tracers to observational systematics has not yet been studied. In this work we analyse the response of void clustering to selection effects. We find for the case of moderate (<20 per cent) incompleteness, void selection based on a constant radius cut yields robust measurements. This is particularly true for BAO-reconstructed galaxy samples, where large-scale void exclusion effects are mitigated. Moreover, we observe for the case of severe (up to 90 per cent) incompleteness – such as can be found at the edges of the radial selection function – that an accurate estimation of the void distribution is necessary for unbiased clustering measurements. In addition, we find that without reconstruction, using a constant threshold under these conditions produces a stronger void exclusion effect that can affect the clustering on large scales. A new void selection criteria dependent on the (local) observed tracer density that maximises the BAO peak significance prevents the aforementioned exclusion features from contaminating the BAO signal. Finally, we verify, with large simulations including light cone evolution, that both void sample definitions (local and constant) yield unbiased and consistent BAO scale measurements.
Eccentricity evolution in gaseous dynamical friction
Authors: Szölgyén Ákos , MacLeod Morgan , Loeb Abraham
Published: May 2022

We analyse how drag forces modify the orbits of objects moving through extended gaseous distributions. We consider how hydrodynamic (surface area) drag forces and dynamical friction (gravitational) drag forces drive the evolution of orbital eccentricity. While hydrodynamic drag forces cause eccentric orbits to become more circular, dynamical friction drag can cause orbits to become more eccentric. We develop a semi-analytic model that accurately predicts these changes by comparing the total work and torque applied to the orbit at periapse and apoapse. We use a toy model of a radial power-law density profile, ρ ∝ r−γ, to determine that there is a critical γ = 3 power index, which separates the eccentricity evolution in dynamical friction: orbits become more eccentric for γ < 3 and circularize for γ > 3. We apply these findings to the infall of a Jupiter-like planet into the envelope of its host star. The hydrostatic envelopes of stars are defined by steep density gradients near the limb and shallower gradients in the interior. Under the influence of gaseous dynamical friction, an infalling object’s orbit will first decrease in eccentricity and then increase. The critical separation that delineates these regimes is predicted by the local density slope and is linearly dependent on polytropic index. More broadly, our findings indicate that binary systems may routinely emerge from common envelope phases with non-zero eccentricities that were excited by the dynamical friction forces that drove their orbital tightening.
The 2021 outburst of the recurrent nova RS Ophiuchi observed in X-rays by the Neil Gehrels Swift Observatory: a comparative study
Authors: Page K L , Beardmore A P , Osborne J P , Munari U , Ness J-U , Evans P A , Bode M F , Darnley M J , Drake J J , Kuin N P M , O’Brien T J , Orio M , Shore S N , Starrfield S , Woodward C E
Published: May 2022

On 2021 August 8, the recurrent nova RS Ophiuchi (RS Oph) erupted again, after an interval of 15.5 yr. Regular monitoring by the Neil Gehrels Swift Observatory began promptly, on August 9.9 (0.37 d after the optical peak), and continued until the source passed behind the Sun at the start of November, 86 d later. Observations then restarted on day 197, once RS Oph emerged from the Sun constraint. This makes RS Oph the first Galactic recurrent nova to have been monitored by Swift throughout two eruptions. Here we investigate the extensive X-ray data sets between 2006 and 2021, as well as the more limited data collected by the European X-ray Observatory Satellite (EXOSAT) in 1985. The hard X-rays arising from shock interactions between the nova ejecta and red giant wind are similar following the last two eruptions. In contrast, the early supersoft source (SSS) in 2021 was both less variable and significantly fainter than in 2006. However, 0.3–1 keV light curves from 2021 reveal a 35 s quasi-periodic oscillation consistent in frequency with the 2006 data. The Swift X-ray spectra from 2021 are featureless, with the soft emission typically being well parametrized by a simple blackbody, while the 2006 spectra showed much stronger evidence for superimposed ionized absorption edges. Considering the data after day 60 following each eruption, during the supersoft phase the 2021 spectra are hotter, with smaller effective radii and lower wind absorption, leading to an apparently reduced bolometric luminosity. We explore possible explanations for the gross differences in observed SSS behaviour between the 2006 and 2021 outbursts.
CSM-Potential: mapping protein interactions and biological ligands in 3D space using geometric deep learning
Authors: Rodrigues Carlos H M , Ascher David B
Published: May 2022

Recent advances in protein structural modelling have enabled the accurate prediction of the holo 3D structures of almost any protein, however protein function is intrinsically linked to the interactions it makes. While a number of computational approaches have been proposed to explore potential biological interactions, they have been limited to specific interactions, and have not been readily accessible for non-experts or use in bioinformatics pipelines. Here we present CSM-Potential, a geometric deep learning approach to identify regions of a protein surface that are likely to mediate protein-protein and protein–ligand interactions in order to provide a link between 3D structure and biological function. Our method has shown robust performance, outperforming existing methods for both predictive tasks. By assessing the performance of CSM-Potential on independent blind tests, we show that our method was able to achieve ROC AUC values of up to 0.81 for the identification of potential protein-protein binding sites, and up to 0.96 accuracy on biological ligand classification. Our method is freely available as a user-friendly and easy-to-use web server and API at http://biosig.unimelb.edu.au/csm_potential.
EPIXplorer: A web server for prediction, analysis and visualization of enhancer-promoter interactions
Authors: Tang Li , Zhong Zhizhou , Lin Yisheng , Yang Yifei , Wang Jun , Martin James F , Li Min
Published: May 2022

Long distance enhancers can physically interact with promoters to regulate gene expression through formation of enhancer-promoter (E-P) interactions. Identification of E-P interactions is also important for profound understanding of normal developmental and disease-associated risk variants. Although the state-of-art predictive computation methods facilitate the identification of E-P interactions to a certain extent, currently there is no efficient method that can meet various requirements of usage. Here we developed EPIXplorer, a user-friendly web server for efficient prediction, analysis and visualization of E-P interactions. EPIXplorer integrates 9 robust predictive algorithms, supports multiple types of 3D contact data and multi-omics data as input. The output from EPIXplorer is scored, fully annotated by regulatory elements and risk single-nucleotide polymorphisms (SNPs). In addition, the Visualization and Downstream module provide further functional analysis, all the output files and high-quality images are available for download. Together, EPIXplorer provides a user-friendly interface to predict the E-P interactions in an acceptable time, as well as understand how the genome-wide association study (GWAS) variants influence disease pathology by altering DNA looping between enhancers and the target gene promoters. EPIXplorer is available at https://www.csuligroup.com/EPIXplorer.
ShapeSorter: a fully probabilistic method for detecting conserved RNA structure features supported by SHAPE evidence
Authors: Tsybulskyi Volodymyr , Meyer Irmtraud M
Published: May 2022

There is an increased interest in the determination of RNA structures in vivo as it is now possible to probe them in a high-throughput manner, e.g. using SHAPE protocols. By now, there exist a range of computational methods that integrate experimental SHAPE-probing evidence into computational RNA secondary structure prediction. The state-of-the-art in this field is currently provided by computational methods that employ the minimum-free energy strategy for prediction RNA secondary structures with SHAPE-probing evidence. These methods, however, rely on the assumption that transcripts in vivo fold into the thermodynamically most stable configuration and ignore evolutionary evidence for conserved RNA structure features. We here present a new computational method, ShapeSorter, that predicts RNA structure features without employing the thermodynamic strategy. Instead, ShapeSorter employs a fully probabilistic framework to identify RNA structure features that are supported by evolutionary and SHAPE-probing evidence. Our method can capture RNA structure heterogeneity, pseudo-knotted RNA structures as well as transient and mutually exclusive RNA structure features. Moreover, it estimates P-values for the predicted RNA structure features which allows for easy filtering and ranking. We investigate the merits of our method in a comprehensive performance benchmarking and conclude that ShapeSorter has a significantly superior performance for predicting base-pairs than the existing state-of-the-art methods.
Detecting TAD-like domains from RNA-associated interactions
Authors: Zhang Yu Wei , Chen Lingxi , Li Shuai Cheng
Published: May 2022

Topologically associated domains (TADs) are crucial chromatin structural units. Evidence has illustrated that RNA–chromatin and RNA–RNA spatial interactions, so-called RNA-associated interactions (RAIs), may be associated with TAD-like domains (TLDs). To decode hierarchical TLDs from RAIs, we proposed SuperTLD, a domain detection algorithm incorporating imputation. We applied SuperTLD on four RAI data sets and compared TLDs with the TADs identified from the corresponding Hi-C datasets. The TLDs and TADs share a moderate similarity of hierarchies ≥ 0.5312 and the finest structures ≥ 0.8295. Comparison between boundaries and domains further demonstrated the novelty of TLDs. Enrichment analysis of epigenetic characteristics illustrated that the novel TLDs exhibit an enriched CTCF by 0.6245 fold change and H3 histone marks enriched within domains. GO analysis on the TLD novel boundaries exhibited enriched diverse terms, revealing TLDs’ formation mechanism related closely to gene regulation.
5NosoAE: a web server for nosocomial bacterial antibiogram investigation and epidemiology survey
Authors: Chen Chih-Chieh , Liu Yen-Yi , Yang Ya-Chu , Hsu Chu-Yi
Published: May 2022

5NosoAE is a webserver that can be used for nosocomial bacterial analysis including the identification of similar strains based on antimicrobial resistance profiles (antibiogram) and the spatiotemporal distribution visualization and phylogenetic analysis of identified strains with similar antibiograms. The extensive use of antibiotics has caused many pathogenic bacteria to develop multiple drug resistance, resulting in clinical infection treatment challenges and posing a major threat to global public health. Relevant studies have investigated the key determinants of antimicrobial resistance in the whole-genome sequence of bacteria. However, a web server is currently not available for performing large-scale strain searches according to antimicrobial resistance profiles and visualizing epidemiological information including the spatiotemporal distribution, antibiogram heatmap, and phylogeny of identified strains. Here, we implemented these functions in the new server, referred to as 5NosoAE. This server accepts the genome sequence file in the FASTA format of five nosocomial bacteria, namely Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterococcus faecium and Staphylococcus aureus for query. All visualizations are implemented in JavaScript and PHP. This server will be useful for physicians and epidemiologists involved in research on infectious disease. The 5NosoAE platform is available at https://nosoae.imst.nsysu.edu.tw.
Aquaculture Molecular Breeding Platform (AMBP): a comprehensive web server for genotype imputation and genetic analysis in aquaculture
Authors: Zeng Qifan , Zhao Baojun , Wang Hao , Wang Mengqiu , Teng Mingxuan , Hu Jingjie , Bao Zhenmin , Wang Yangfan
Published: May 2022

It is of vital importance to understand the population structure, dissect the genetic bases of performance traits, and make proper strategies for selection in breeding programs. However, there is no single webserver covering the specific needs in aquaculture. We present Aquaculture Molecular Breeding Platform (AMBP), the first web server for genetic data analysis in aquatic species of farming interest. AMBP integrates the haplotype reference panels of 18 aquaculture species, which greatly improves the accuracy of genotype imputation. It also supports multiple tools to infer genetic structures, dissect the genetic architecture of performance traits, estimate breeding values, and predict optimum contribution. All the tools are coherently linked in a web-interface for users to generate interpretable results and evaluate statistical appropriateness. The webserver supports standard VCF and PLINK (PED, MAP) files, and implements automated pipelines for format transformation and visualization to simplify the process of analysis. As a demonstration, we applied the webserver to Pacific white shrimp and Atlantic salmon datasets. In summary, AMBP constitutes comprehensive resources and analytical tools for exploring genetic data and guiding practical breeding programs. AMBP is available at http://mgb.qnlm.ac.
MO119: Lupus Nephritis in Males: About 34 Cases
Authors: Afifi Rania , Elkhayat Ss , Medkouri G , Mtioui N , Zamd M , Ramdani B , Benghanem M
Published: May 2022

BACKGROUND AND AIMS

Lupus nephritis (LN) is one of the most serious manifestations of systemic lupus erythematosus (SLE), affecting mainly young women, but can also affect men. It refers to the development of intrarenal tissue inflammation responsible for various damage at this level: glomerular, vascular and/or tubulointerstitial lesions.

This complication, which can be inaugural, occurs in the majority of cases early in the history of the disease, and constitutes a major evolutionary turning point, which can lead to end-stage chronic renal failure in 5–10% of cases.

The aim of our study was to analyse the different characteristics of NL in humans, since the latter is little studied due to the rarity of cases.

METHOD

We conducted a descriptive retrospective study at the nephrology departments of the Ibn Rochd University Hospital in Casablanca, from January 2011 to August 2021 (i.e. 10 years) on LN. All male patients (34 cases) who developed LN confirmed on renal biopsy.

RESULTS

The average age of the patients was 29.41 years with extremes ranging from 15 to 56 years among them five black patients. The circumstance of discovery of LN was edematous syndrome in 46.87%, nephrotic syndrome 37.5% and renal failure in 15.62% of cases. The renal manifestations were made of arterial hypertension in 21.87% of cases, and haematuria in 15.62% of cases. The extrarenal manifestations were articular in 37.5% of cases, cutaneous in 56.25% of cases and 40.62% of cases had general signs. Biologically, on the blood count, haemolytic anaemia was observed in 87.5% of cases, lymphopenia in 31.25% of cases and thrombocytopaenia in 40.62%, while AANs were positive in 96.87% and anti-DNA antibody were positive in 93.75%. Hypocomplementemia was objectified in 84.37%. Histologically: according to the World Health Organization classification of LN, we have reported: LN class I in a single patient, i.e. 3.12%, and LN class III in 12.5% of cases, LN class IV in 53.12% and LN class V in 31.25%, while the combination of class V and III was seen in one patient and the combination of class IV and V in three cases. Concerning the evolution 34.37% progressed well with complete remission, 31.2% of patients relapsed, while three patients progressed to end-stage kidney disease (ESKD) and all of three from black. The evolution was also marked by death in eight patients; among them four were black.

CONCLUSION

Lupus disease is more aggressive in men and is characterized by a higher rate of complications, including kidney damage. In our study, we were able to deduce that LN in the black race has a bad prognosis.
MO139: Advance Care Planning in Hemodialysis: A Challenge for the Italian Nephrology
Authors: Simone Giuseppina , Toccafondi Alessandro , Ferro Giuseppe , Brogi Lorenzo , Gori Gabriele , Somma Chiara , Tsalouchos Aris , Mehmetaj Alma , Semeraro Francesca , Laudicina Selene , Dattolo Pietro
Published: May 2022

BACKGROUND

Advance care planning (ACP) enables competent patients to define goals and preferences for future treatments and care, to discuss these goals and preferences with relatives, and if appropriate to record these preferences [1]. After many years of political and social debates, in December 2017 the first advance directive and care planning legislation was approved in Italy. In the last years, several national recommendations released by political institutions and medical associations have underlined the importance of conducting ACP with chronic patients, included dialyses patients. Nevertheless, citizens’ awareness of these issues is scarce as well as the integration of the ACP process into clinical routine [2].

METHOD

Since November 2020, our nephrology unit adopted a protocol aimed to conduct ACP interventions with dialysis patients. Firstly, all patients were informed about the possibility to taking part in one or more ACP conversations with their nephrologist. Secondly, a semi-structured guide to the conversation was created in order to support physicians in conducting the ACP intervention. The guide is divided into three sections: (1) exploring patient's understanding of the disease and his/her hopes and life goals; (2) patient's social relationships; (3) preferences for future treatments and care (e.g. CPR, dialysis, palliative care, etc). Finally, patients along with nephrologist and their relatives can document their preferences.

RESULTS

Of 110 haemodialysis patients, 40 treated in our centre asked for an ACP intervention and filled-in an advance directive. Specifically, no patients required an immediate discontinuation of dialysis; nevertheless, 70% of them stated that would not like to continue with dialysis in case he/she was no longer able to self-determine (e.g. permanent loss of capacity to communicate with others). Most of patients (90%) have appointed a personal representative (usually their partner). In the eventuality of cardiac arrest, 55% of patients asked for cardiopulmonary resuscitation. Pain control and palliative care was the overall most cited topic. The fear of being a burden on family members has been frequently expressed by not independent patients. Regarding the last phase of life, 75% of patients expressed the desire to stay at home, the others in hospice.

CONCLUSION

ACP process is very recent in Italy and not well known by patients and healthcare providers (HCPs). As a result, discussions about future treatments and care are rarely included in the clinical routine with haemodialysis patients. Training of HCPs on these issues as well as the use of procedures tailored to the Italian context for conducting ACP interventions is needed.