bluuebunny/crossref_metadata_2025 huggingface dataset:
Oral daily PTH(1-34) tablets (EB613) in postmenopausal women with low BMD or osteoporosis: a randomized, placebo-controlled, 6-month, phase 2 study
Authors: Tripto-Shkolnik Liana , Szalat Auryan , Tsvetov Gloria , Rouach Vanessa , Sternberg Chana , Hoppe Anke , Burshtein Gregory , Galitzer Hillel , Toledano Miranda , Harari Gil , Santora Arthur C , Cosman Felicia
Published: April 2024

Anabolic treatment is indicated for high and very-high risk patients with osteoporosis, but acceptance is limited because current anabolic medications require subcutaneous injections. The purpose of this study was to assess the effects of a novel orally administered PTH tablet on serum markers of bone formation (PINP and osteocalcin), bone resorption (crosslinked C-telopeptide [CTX]), BMD, and safety in postmenopausal women with low BMD or osteoporosis. In this 6-mo, double-blind, placebo-controlled study, 161 patients were randomized to oral PTH tablets containing 0.5, 1.0, 1.5, or 2.5 mg or placebo daily. Biochemical markers were assessed at 1, 2, 3, and 6 mo and BMD of LS, TH, and FN was measured at 6 mo. Biochemical marker changes were dose dependent with minimal or no effect at the 2 lowest doses. At the highest dose (2.5 mg once daily), serum PINP and OC levels increased 30% within 1 mo after oral PTH initiation (P < .0001), remained elevated through 3 mo, and were back to baseline at 6 mo. In contrast, serum CTX levels declined 16% and 21% below baseline at 3 and 6 mo, respectively (both P ≤ .02). At 6 mo, 2.5 mg tablets increased mean BMD vs placebo of the LS by 2.7%, TH by 1.8%, and FN by 2.8% (all P ≤ .01). There were no drug-related serious adverse events. The most common adverse events were headache, nausea, and dizziness. In contrast to subcutaneous PTH, the oral PTH tablet appears to increase BMD rapidly by the dual mechanism of stimulating formation and inhibiting bone resorption. This might be the first effective oral anabolic alternative to subcutaneous administration for the treatment of low BMD or osteoporosis.
The determinant and a factorization of a Toeplitz matrix with some type of Horadam numbers entries
Authors: da Fonseca Carlos M , Kızılateş Can , Terzioğlu Nazlıhan
Published: April 2024

In this note, we define a symmetric Toeplitz matrix whose entries are from a particular Horadam sequence. We provide the determinant, the inverse and a factorization for such matrices and their special cases. These matrices are always nonsingular and their inverses are pentadiagonal matrices.
Application of the surface engineered recombinant Escherichia coli to the industrial battery waste solution for lithium recovery
Authors: Jeong Jaehoon , Selvamani Vidhya , Maruthamuthu Murali kannan , Arulsamy Kulandaisamy , Hong Soon Ho
Published: April 2024

Escherichia coli were engineered to selectively adsorb and recover lithium from the environment by employing a bacterial cell surface display strategy. Lithium binding peptide (LBP1) was integrated into the Escherichia coli membrane protein OmpC. The effect of environmental conditions on the adsorption of lithium by a recombinant strain was evaluated, and lithium particles on the cellular surface were analyzed by FE-SEM and XRD. To elevate the lithium adsorption, dimeric, trimeric, and tetrameric repeats of the LBP1 peptide were constructed and displayed on the surface of E. coli. The constructed recombinant E. coli displaying the LBP1 trimer was applied to real industrial lithium battery wastewater to recover lithium.
TP53-associated early breast cancer: new observations from a large cohort
Authors: Sandoval Renata L , Bottosso Michele , Tianyu Li , Polidorio Natalia , Bychkovsky Brittany L , Verret Benjamin , Gennari Alessandra , Cahill Sophie , Achatz Maria Isabel , Caron Olivier , Imbert-Bouteille Marion , Noguès Catherine , Mawell Kara N , Fortuno Cristina , Spurdle Amanda B , Tayob Nabihah , Andre Fabrice , Garber Judy E
Published: April 2024

Background

A recent large, well-annotated international cohort of patients with Li-Fraumeni syndrome and early-stage breast cancer was examined for shared features.

Methods

This multicenter cohort study included women with a germline TP53 pathogenic or likely pathogenic variant and nonmetastatic breast cancer diagnosed between 2002 and 2022. Clinical and genetic data were obtained from institutional registries and clinical charts. Descriptive statistics were used to summarize proportions, and differences were assessed using χ2 or Wilcoxon rank sum tests. Metachronous contralateral breast cancer risk, radiation-induced sarcoma risk, and recurrence-free survival were analyzed using the Kaplan-Meier methodology.

Results

Among 227 women who met study criteria, the median age of first breast cancer diagnosis was 37 years (range = 21-71), 11.9% presented with bilateral synchronous breast cancer, and 18.1% had ductal carcinoma in situ only. In total, 166 (73.1%) patients underwent mastectomies, including 67 bilateral mastectomies as first breast cancer surgery. Among those patients with retained breast tissue, the contralateral breast cancer rate was 25.3% at 5 years. Among 186 invasive tumors, 72.1% were stages I to II, 48.9% were node negative, and the most common subtypes were hormone receptor-positive/HER2-negative (40.9%) and hormone receptor positive/HER2 positive (34.4%). At a median follow-up of 69.9 months (interquartile range = 32.6-125.9), invasive hormone receptor–positive/HER2-negative disease had the highest recurrence risk among the subtypes (5-year recurrence-free survival = 61.1%, P = .001). Among those who received radiation therapy (n = 79), the 5-year radiation-induced sarcoma rate was 4.8%.

Conclusion

We observed high rates of ductal carcinoma in situ, hormone receptor–positive, and HER2-positive breast cancers, with a worse outcome in the hormone receptor–positive/HER2-negative luminal tumors, despite appropriate treatment. Confirmation of these findings in further studies could have implications for breast cancer care in those with Li-Fraumeni syndrome.
Identification of hub genes involved in gibberellin-regulated elongation of coleoptiles of rice seeds germinating under submerged conditions
Authors: Hu Yunfei , Ma Mingqing , Zhao Wenlong , Niu Pengwei , Li Rongbai , Luo Jijing
Published: April 2024

Rapid elongation of coleoptiles from rice seeds to reach the water surface enables plants to survive submergence stress and therefore plays a crucial role in allowing direct seeding in rice cultivation. Gibberellin (GA) positively influences growth in rice, but the molecular mechanisms underlying its regulation of coleoptile elongation under submerged conditions remain unclear. In this study, we performed a weighted gene co-expression network analysis to conduct a preliminarily examination of the mechanisms. Four key modules were identified with high correlations to the GA regulation of submergence tolerance. The genes within these modules were mainly involved in the Golgi apparatus and carbohydrate metabolic pathways, suggesting their involvement in enhancing submergence tolerance. Further analysis of natural variation revealed that the specific hub genes Os03g0337900, Os03g0355600, and Os07g0638400 exhibited strong correlations with subspecies divergence of the coleoptile elongation phenotype. Consistent with this analysis, mutation of Os07g0638400 resulted in a lower germination potential and a stronger inhibition of coleoptile elongation under submerged conditions. The hub genes identified in this study provide new insights into the molecular mechanisms underlying GA-dependent tolerance to submergence stress in rice, and a potential basis for future modification of rice germplasm to allow for direct seeding.
Accounting for photosystem I photoinhibition sheds new light on seasonal acclimation strategies of boreal conifers
Authors: Grebe Steffen , Porcar-Castell Albert , Riikonen Anu , Paakkarinen Virpi , Aro Eva-Mari
Published: April 2024

The photosynthetic acclimation of boreal evergreen conifers is controlled by regulatory and photoprotective mechanisms that allow conifers to cope with extreme environmental changes. However, the underlying dynamics of photosystem II (PSII) and photosystem I (PSI) remain unresolved. Here, we investigated the dynamics of PSII and PSI during the spring recovery of photosynthesis in Pinus sylvestris and Picea abies using a combination of chlorophyll a fluorescence, P700 difference absorbance measurements, and quantification of key thylakoid protein abundances. In particular, we derived a new set of PSI quantum yield equations, correcting for the effects of PSI photoinhibition. Using the corrected equations, we found that the seasonal dynamics of PSII and PSI photochemical yields remained largely in balance, despite substantial seasonal changes in the stoichiometry of PSII and PSI core complexes driven by PSI photoinhibition. Similarly, the previously reported seasonal up-regulation of cyclic electron flow was no longer evident, after accounting for PSI photoinhibition. Overall, our results emphasize the importance of considering the dynamics of PSII and PSI to elucidate the seasonal acclimation of photosynthesis in overwintering evergreens. Beyond the scope of conifers, our corrected PSI quantum yields expand the toolkit for future studies aimed at elucidating the dynamic regulation of PSI.
Biofilm-producing Escherichia coli O104:H4 overcomes bile salts toxicity by expressing virulence and resistance proteins
Authors: Machado Maxsueli Aparecida Moura , Chapartegui-González Itziar , Castro Vinicius Silva , Figueiredo Eduardo Eustáquio de Souza , Conte-Junior Carlos Adam , Torres Alfredo G
Published: April 2024

We investigated bile salts’ ability to induce phenotypic changes in biofilm production and protein expression of pathogenic Escherichia coli strains. For this purpose, 82 pathogenic E. coli strains isolated from humans (n = 70), and animals (n = 12), were examined for their ability to form biofilms in the presence or absence of bile salts. We also identified bacterial proteins expressed in response to bile salts using sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-electrophoresis) and liquid chromatography-mass spectrometry (LC-MS/MS). Lastly, we evaluated the ability of these strains to adhere to Caco-2 epithelial cells in the presence of bile salts. Regarding biofilm formation, two strains isolated from an outbreak in Republic of Georgia in 2009 were the only ones that showed a high and moderate capacity to form biofilm in the presence of bile salts. Further, we observed that those isolates, when in the presence of bile salts, expressed different proteins identified as outer membrane proteins (i.e. OmpC), and resistance to adverse growth conditions (i.e. F0F1, HN-S, and L7/L12). We also found that these isolates exhibited high adhesion to epithelial cells in the presence of bile salts. Together, these results contribute to the phenotypic characterization of E. coli O104: H4 strains.
Using CHROMagar™ STEC medium exclusively does not recover all clinically relevant Shiga toxin-producing Escherichia coli in Aotearoa, New Zealand
Authors: Rivas Lucia , Duncan David , Wang Jing , Miller Hilary , Wright Jackie
Published: April 2024

Diagnostic laboratories in Aotearoa, New Zealand (NZ) refer cultures from faecal samples positive for Shiga toxin genes to the national Enteric Reference Laboratory for isolation of Shiga toxin-producing Escherichia coli (STEC) for epidemiological typing. As there was variation in the culture media being referred, a panel of 75 clinical isolates of STEC, representing 28 different serotypes, was used to assess six commercially available media and provide guidance to clinical laboratories. Recommendations were subsequently tested for a 3-month period, where STEC isolations and confirmations were assessed by whole genome sequencing analysis against the culture media referred. CHROMagar™ STEC (CH-STEC; CHROMagar Microbiology, Paris, France) or CH-STEC plus cefixime-tellurite sorbitol MacConkey agar was confirmed inferior to CH-STEC plus blood agar with vancomycin, cefsulodin, and cefixime (BVCC). The former resulted in fewer STEC types (n = 18) being confirmed compared to those from a combination of CH-STEC and BVCC (n = 42). A significant (P < .05) association with an STEC’s ability to grow on CH-STEC and the presence of the ter gene cluster, and eae was observed. Culturing screen positive STEC samples onto both CH-STEC and BVCC ensures a consistently higher recovery of STEC from all clinical samples in NZ than CH-STEC alone.
Mo than meets the eye: genomic insights into molybdoenzyme diversity of Seleniivibrio woodruffii strain S4T
Authors: Louie Tiffany S , Kumar Anil , Bini Elisabetta , Häggblom Max M
Published: April 2024

Seleniivibrio woodruffii strain S4T is an obligate anaerobe belonging to the phylum Deferribacterota. It was isolated for its ability to respire selenate and was also found to respire arsenate. The high-quality draft genome of this bacterium is 2.9 Mbp, has a G+C content of 48%, 2762 predicted genes of which 2709 are protein-coding, and 53 RNA genes. An analysis of the genome focusing on the genes encoding for molybdenum-containing enzymes (molybdoenzymes) uncovered a remarkable number of genes encoding for members of the dimethylsulfoxide reductase family of proteins (DMSOR), including putative reductases for selenate and arsenate respiration, as well as genes for nitrogen fixation. Respiratory molybdoenzymes catalyze redox reactions that transfer electrons to a variety of substrates that can act as terminal electron acceptors for energy generation. Seleniivibrio woodruffii strain S4T also has essential genes for molybdate transporters and the biosynthesis of the molybdopterin guanine dinucleotide cofactors characteristic of the active centers of DMSORs. Phylogenetic analysis revealed candidate respiratory DMSORs spanning nine subfamilies encoded within the genome. Our analysis revealed the untapped potential of this interesting microorganism and expanded our knowledge of molybdoenzyme co-occurrence.
Safety and pharmacokinetics of antifungal agent VT-1598 and its primary metabolite, VT-11134, in healthy adult subjects: phase 1, first-in-human, randomized, double-blind, placebo-controlled study of single-ascending oral doses of VT-1598
Authors: Gu Kenan , Spitz Robert , Hammett Erin , Jaunarajs Anna , Ghazaryan Varduhi , Garvey Edward P , Degenhardt Thorsten
Published: April 2024

VT-1598 is a novel fungal CYP51 inhibitor and 1-tetrazole-based antifungal drug candidate with improved selectivity minimizing off-target binding to and inhibition of human CYP450 enzymes. Data are presented from this first clinical study in the evaluation of the safety and pharmacokinetic (PK) of single ascending doses of 40, 80, 160, 320, and 640 mg VT-1598, comprising a 160 mg cohort in both fasting and fed states. Eight healthy adults per dose were randomized to receive either oral VT-1598 or placebo (3:1). Over the dose range, exposures were with relatively high variation. The maximum plasma concentrations (Cmax) for VT-1598 were 31.00–279.4 ng/ml and for its primary metabolite, VT-11134, were 27.80–108.8 ng/ml. The plasma area under the concentration–time curve to the last measurable concentration (AUC0–last) for VT-1598 were 116.1–4507 ng*h/ml, and for VT-11134 were 1140–7156 ng*h/ml. The dose proportionality was inconclusive based on the results of the power model. The peak concentration time (Tmax) was 4–5 h for VT-1598 and for VT-11134. Half-life was 103–126 h for VT-11134. After food intake, Cmax of VT-1598 increased by 44% (geometric mean ratio (GMR), 1.44; 90%CI [0.691, 2.19]) and AUC0–last by 126% (GMR, 2.26; 90%CI [1.09, 3.44]), while exposure of VT-11134 was decreased 23% for Cmax (GMR, 0.77; 90%CI [0.239, 1.31]) and unchanged for AUC0–last (GMR, 1.02; 90%CI [0.701, 1.33]). Neither VT-1598 nor VT-11134 were detected in urine. No serious adverse events (AEs) or AEs leading to early termination were observed. The safety and PK profiles of VT-1598 support its further clinical development.
Aflatoxin profiles of Aspergillus flavus isolates in Sudanese fungal rhinosinusitis
Authors: Zhou Shaoqin , Ismail Mawahib A I , Aimanianda Vishukumar , de Hoog G Sybren , Kang Yingqian , Ahmed Sarah A
Published: April 2024

Aspergillus flavus is a commonly encountered pathogen responsible for fungal rhinosinusitis (FRS) in arid regions. The species is known to produce aflatoxins, posing a significant risk to human health. This study aimed to investigate the aflatoxin profiles of A. flavus isolates causing FRS in Sudan. A total of 93 clinical and 34 environmental A. flavus isolates were studied. Aflatoxin profiles were evaluated by phenotypic (thin-layer and high-performance chromatography) and genotypic methods at various temperatures and substrates. Gene expression of aflD and aflR was also analyzed. A total of 42/93 (45%) isolates were positive for aflatoxin B1 and AFB2 by HPLC. When the incubation temperature changed from 28°C to 36°C, the number of positive isolates decreased to 41% (38/93). Genetic analysis revealed that 85% (79/93) of clinical isolates possessed all seven aflatoxin biosynthesis-associated genes, while 27% (14/51) of non-producing isolates lacked specific genes (aflD/aflR/aflS). Mutations were observed in aflS and aflR genes across both aflatoxin-producers and non-producers. Gene expression of aflD and aflR showed the highest expression between the 4th and 6th days of incubation on the Sabouraud medium and on the 9th day of incubation on the RPMI (Roswell Park Memorial Institute) medium. Aspergillus flavus clinical isolates demonstrated aflatoxigenic capabilities, influenced by incubation temperature and substrate. Dynamic aflD and aflR gene expression patterns over time enriched our understanding of aflatoxin production regulation. The overall findings underscored the health risks of Sudanese patients infected by this species, emphasizing the importance of monitoring aflatoxin exposure.
SN 2015da: late-time observations of a persistent superluminous Type IIn supernova with post-shock dust formation
Authors: Smith Nathan , Andrews Jennifer E , Milne Peter , Filippenko Alexei V , Brink Thomas G , Kelly Patrick L , Yuk Heechan , Jencson Jacob E
Published: April 2024

We present photometry and spectroscopy of the slowly evolving superluminous Type IIn supernova (SN) 2015da. SN 2015da is extraordinary for its very high peak luminosity, and also for sustaining a high luminosity for several years. Even at 8 yr after explosion, SN 2015da remains as luminous as the peak of a normal SN II-P. The total radiated energy integrated over this time period (with no bolometric correction) is at least $1.6 \times 10^{51}$ erg (or 1.6 FOE). Including a mild bolometric correction, adding kinetic energy of the expanding cold dense shell of swept-up circumstellar material (CSM), and accounting for asymmetry, the total explosion kinetic energy was likely 5–10 FOE. Powering the light curve with CSM interaction requires an energetic explosion and 20 M$_{\odot }$ of H-rich CSM, which in turn implies a massive progenitor system $\gt $30 M$_{\odot }$. Narrow P Cyg features show steady CSM expansion at 90 km s$^{-1}$, requiring a high average mass-loss rate of $\sim$0.1 M$_{\odot }$ yr$^{-1}$ sustained for two centuries before explosion (although ramping up toward explosion time). No current theoretical model for single-star pre-SN mass-loss can account for this. The slow CSM, combined with broad wings of H $\alpha$ indicating H-rich material in the unshocked ejecta, disfavours a pulsational pair instability model for the pre-SN mass-loss. Instead, violent pre-SN binary interaction is a likely culprit. Finally, SN 2015da exhibits the characteristic asymmetric blueshift in its emission lines from shortly after peak until the present epoch, adding another well-studied superluminous SNe IIn with unambiguous evidence of post-shock dust formation.
NSCs from groups to clusters: a catalogue of dwarf galaxies in the Shapley supercluster and the role of environment in galaxy nucleation
Authors: Zanatta Emílio , Sánchez-Janssen Rubén , de Souza Rafael S , Chies-Santos Ana L , Blakeslee John P
Published: April 2024

Nuclear star clusters (NSCs) are dense star clusters located at the centre of galaxies spanning a wide range of masses and morphologies. Analysing NSC occupation statistics in different environments provides an invaluable window into investigating early conditions of high-density star formation and mass assembly in clusters and group galaxies. We use HST/ACS deep imaging to obtain a catalogue of dwarf galaxies in two galaxy clusters in the Shapley supercluster: the central cluster Abell 3558 and the northern Abell 1736a. The Shapley region is an ideal laboratory to study nucleation as it stands as the highest mass concentration in the nearby Universe. We investigate the NSC occurrence in quiescent dwarf galaxies as faint as MI = −10 mag and compare it with all other environments where nucleation data is available. We use galaxy cluster/group halo mass as a proxy for the environment and employ a Bayesian logistic regression framework to model the nucleation fraction (fn) as a function of galaxy luminosity and environment. We find a notably high fn in Abell 3558: at MI ≈ −13.1 mag, half the galaxies in the cluster host NSCs. This is higher than in the Virgo and Fornax clusters but comparable to the Coma Cluster. On the other hand, the fn in Abell 1736a is relatively lower, comparable to groups in the local volume. We find that the probability of nucleation varies with galaxy luminosity remarkably similarly in galaxy clusters. These results reinforce previous findings of the important role of the environment in NSC formation/growth.
Generic gravito-magnetic clock effects
Authors: Li Kaye Jiale , Wu Kinwah , Younsi Ziri , Teixeira Joana , Singh Dinesh
Published: April 2024

General relativity predicts that two counter-orbiting clocks around a spinning mass differ in the time required to complete the same orbit. The difference in these two values for the orbital period is generally referred to as the gravito-magnetic (GM) clock effect. It has been proposed to measure the GM clock effect using atomic clocks carried by satellites in prograde and retrograde orbits around the Earth. The precision and stability required for satellites to accurately perform this measurement remains a challenge for current instrumentation. One of the most accurate clocks in the Universe is a millisecond pulsar, which emits periodic radio pulses with high stability. Timing of the pulsed signals from millisecond pulsars has proven to be very successful in testing predictions of general relativity and the GM clock effect is potentially measurable in binary systems. In this work, we derive the generic GM clock effect by considering a slowly spinning binary system on an elliptical orbit, with both arbitrary mass ratio and arbitrary spin orientations. The spin–orbit interaction introduces a perturbation to the orbit, causing the orbital plane to precess and nutate. We identify several different contributions to the clock effects: the choice of spin supplementary condition and the observer-dependent definition of a full revolution and ‘nearly identical’ orbits. We discuss the impact of these subtle definitions on the formula for GM clock effects and show that most of the existing formulae in the literature can be recovered under appropriate assumptions.
Pulsation phases and mode identification of tidally excited oscillations in fourteen Kepler Heartbeat Stars
Authors: Li Min-Yu , Qian Sheng-Bang , Zhu Li-Ying , Guo Zhao , Liao Wen-Ping , Zhao Er-Gang , Shi Xiang-Dong , Li Fu-Xing , Sun Qi-Bin
Published: April 2024

Tidally excited oscillations (TEOs) in Heartbeat Stars (HBSs) are an essential probe of the internal properties of the systems, but their potential has yet to be fully exploited. Based on the orbital parameters of TEO candidates from our previous works, we identify the pulsation phases and amplitudes of TEOs in 14 Kepler HBSs. Most pulsation phases of most systems can be explained by the dominant being l = 2, m = 0, or ±2 spherical harmonic, assuming that the spin and orbital axes are aligned, and the pulsations are adiabatic and standing waves. The largest deviation (>6σ) occurs in KIC 8459354, which can be explained by the spin-orbit misalignment, and KIC 5877364 has a similar scenario. For KIC 11122789, almost half of the harmonics show large deviations; we cautiously suggest that these harmonics may not be considered TEO candidates. A similar scenario also exists in KIC 6290740. This phases and mode identification approach can also be used inversely to verify the TEO candidates derived by the Fourier analysis. Furthermore, the harmonics with large deviations (>2σ) in KIC 4377638, KIC 5090937, and KIC 11403032 can be expected to be travelling waves rather than standing waves. In addition, we also suggest that the apsidal motion could cause large deviations in TEO phases from theoretical values.
Enabling unsupervised discovery in astronomical images through self-supervised representations
Authors: Mohale Koketso , Lochner Michelle
Published: April 2024

Unsupervised learning, a branch of machine learning that can operate on unlabelled data, has proven to be a powerful tool for data exploration and discovery in astronomy. As large surveys and new telescopes drive a rapid increase in data size and richness, these techniques offer the promise of discovering new classes of objects and of efficient sorting of data into similar types. However, unsupervised learning techniques generally require feature extraction to derive simple but informative representations of images. In this paper, we explore the use of self-supervised deep learning as a method of automated representation learning. We apply the algorithm Bootstrap Your Own Latent to Galaxy Zoo DECaLS images to obtain a lower dimensional representation of each galaxy, known as features. We briefly validate these features using a small supervised classification problem. We then move on to apply an automated clustering algorithm, demonstrating that this fully unsupervised approach is able to successfully group together galaxies with similar morphology. The same features prove useful for anomaly detection, where we use the framework astronomaly to search for merger candidates. While the focus of this work is on optical images, we also explore the versatility of this technique by applying the exact same approach to a small radio galaxy data set. This work aims to demonstrate that applying deep representation learning is key to unlocking the potential of unsupervised discovery in future data sets from telescopes such as the Vera C. Rubin Observatory and the Square Kilometre Array.
MRI turbulence in vertically stratified accretion discs at large magnetic Prandtl numbers
Authors: Held Loren E , Mamatsashvili George , Pessah Martin E
Published: April 2024

The discovery of the first binary neutron star merger, GW170817, has spawned a plethora of global numerical relativity simulations. These simulations are often ideal (with dissipation determined by the grid) and/or axisymmetric (invoking ad hoc mean-field dynamos). However, binary neutron star mergers (similar to X-ray binaries and active galactic nuclei inner discs) are characterized by large magnetic Prandtl numbers, $\rm Pm$, (the ratio of viscosity to resistivity). $\rm Pm$ is a key parameter determining dynamo action and dissipation but it is ill-defined (and likely of order unity) in ideal simulations. To bridge this gap, we investigate the magnetorotational instability (MRI) and associated dynamo at large magnetic Prandtl numbers using fully compressible, three-dimensional, vertically stratified, isothermal simulations of a local patch of a disc. We find that, within the bulk of the disc (z ≲ 2H, where H is the scale-height), the turbulent intensity (parametrized by the stress-to-thermal-pressure ratio α), and the saturated magnetic field energy density, Emag, produced by the MRI dynamo, both scale as a power with Pm at moderate Pm (4 ≲ Pm ≲ 32): Emag ∼ Pm0.74 and α ∼ Pm0.71, respectively. At larger Pm (≳ 32), we find deviations from power-law scaling and the onset of a plateau. Compared to our recent unstratified study, this scaling with Pm becomes weaker further away from the disc mid-plane, where the Parker instability dominates. We perform a thorough spectral analysis to understand the underlying dynamics of small-scale MRI-driven turbulence in the mid-plane and of large-scale Parker-unstable structures in the atmosphere.
General upper limit on the electric charge of Sgr A* in the Reissner–Nordström metric
Authors: Mishra Ruchi , Vieira Ronaldo S S , Kluźniak Włodek
Published: April 2024

In general relativity, the gravitational field of an electrically charged, non-rotating, spherically symmetric body is described by the Reissner–Nordström (RN) metric. Depending on the charge to mass ratio, the solution describes a black hole or a naked singularity. In the naked-singularity regime, a general property of this metric is the existence of a radius, known as the zero-gravity radius, where a test particle would remain at rest. As a consequence of repulsive gravity there is no circular orbit inside this radius, and at least a part of any quasi-stable structure must necessarily lie outside of it. Assuming the iconic torus in the compact source Sgr A* at the Galactic centre observed by the Event Horizon Telescope (EHT) to be the image of a quasi-stationary fluid structure, we provide rigorous constraints in the RN metric on the electric charge-to-mass ratio Q/M of Sgr A*. A comparison between the EHT observations and the space–time zero-gravity radius provides the most conservative limit on the charge of Sgr A* to be |Q/M| < 2.32 in geometrized units. A charged naked singularity respecting this charge-to-mass constraint is consistent with the current EHT observations, if the image is not interpreted as a photon ring.
xGASS: the scatter of the H i–halo mass relation of central galaxies
Authors: Saraf Manasvee , Cortese Luca , Wong O Ivy , Catinella Barbara , Janowiecki Steven , Hardwick Jennifer A
Published: April 2024

Empirical studies of the relationship between baryonic matter in galaxies and the gravitational potential of their host haloes are important to constrain our theoretical framework for galaxy formation and evolution. One such relation, between the atomic hydrogen (H i) mass of central galaxies (MH i,c) and the total mass of their host haloes (Mhalo), has attracted significant interest in the last few years. In this work, we use the extended GALEX Arecibo SDSS Survey to examine the scatter of the H i–halo mass relation for a representative sample of central galaxies. Our findings reveal a flat median relation at $\mathrm{ log}_{10}(M_{\rm {H\,{\small I},c}}/\rm {M}_{\odot }) \approx 9.40$, across $11.1 \lt \mathrm{ log}_{10}(M_{\rm {halo}}/{{\rm M}_{\odot }}) \lt 14.1$. This flat relation stems from the statistical dominance of star-forming, disc galaxies at low Mhalo in combination with the increasing prevalence of passive, high stellar concentration systems at higher Mhalo. The scatter of this relation and the stellar specific angular momentum of centrals have a strong link (Spearman’s rank correlation coefficient ≥0.5). Comparisons with simulations suggest that the kinematic state of host haloes may be primarily driving this scatter. Our findings highlight that the H i–halo mass parameter space is too complex to be completely represented by simple median or average relations and we show that tensions with previous works are most likely due to selection biases. We recommend that future observational studies, and their comparisons with theoretical models, bin central galaxies also by their secondary properties to enable a statistically robust understanding of the processes regulating the cold gas content within central galaxies of dark matter haloes.
New Herbig–Haro objects associated with embedded sources
Authors: Movsessian T A , Magakian T Yu , Reipurth B , Andreasyan H R
Published: April 2024

We continue to present the results of the Byurakan Narrow Band Imaging Survey (BNBIS). The main goal of this survey is to search for Herbig–Haro (HH) objects and jets in Galactic dark clouds. In this work we present the results of the search in the vicinity of infrared sources that are bright in the WISE survey and embedded in the dark clouds. The survey is performed with the 1-m Schmidt telescope of Byurakan Observatory, lately equipped with a new CCD detector, which allows to obtain one square degree images of the sky in various filters. Narrow-band filters were used to obtain H α and [S ii] images, and a medium-width filter was used for the continuum imaging. New HH flows and knots were found near six embedded IR sources, which constitutes a significant proportion of the objects observed. At least two of the newly found HH flows (HH 1226 and HH 1227) lie in isolated dark clouds, thus pointing to active star formation in these regions. Other flows are also located in detached and dense globules or filaments. The length of the HH 1228 flow is about 1 pc; it has also a molecular hydrogen counterpart of the same extension. Coordinates, charts, detailed descriptions and distance estimates are provided. The lower limits of bolometric luminosities of the source stars are typical for low-mass young stellar objects.
Particle-in-cell simulations of the magnetorotational instability in stratified shearing boxes
Authors: Sandoval Astor , Riquelme Mario , Spitkovsky Anatoly , Bacchini Fabio
Published: April 2024

The magnetorotational instability (MRI) plays a crucial role in regulating the accretion efficiency in astrophysical accretion discs. In low-luminosity discs around black holes, such as Sgr A* and M87, Coulomb collisions are infrequent, making the MRI physics effectively collisionless. The collisionless MRI gives rise to kinetic plasma effects that can potentially affect its dynamic and thermodynamic properties. We present 2D and 3D particle-in-cell (PIC) plasma simulations of the collisionless MRI in stratified discs using shearing boxes with net vertical field. We use pair plasmas, with initial β = 100 and concentrate on subrelativistic plasma temperatures (kBT ≲ mc2). Our 2D and 3D runs show disc expansion, particle and magnetic field outflows, and a dynamo-like process. They also produce magnetic pressure dominated discs with (Maxwell stress dominated) viscosity parameter α ∼ 0.5–1. By the end of the simulations, the dynamo-like magnetic field tends to dominate the magnetic energy and the viscosity in the discs. Our 2D and 3D runs produce fairly similar results, and are also consistent with previous 3D MHD (magnetohydrodynamic) simulations. Our simulations also show non-thermal particle acceleration, approximately characterized by power-law tails with temperature-dependent spectral indices − p. For temperatures $k_\mathrm{ B}T \sim 0.05-0.3\, mc^2$, we find p ≈ 2.2–1.9. The maximum accelerated particle energy depends on the scale separation between MHD and Larmor-scale plasma phenomena in a way consistent with previous PIC results of magnetic reconnection-driven acceleration. Our study constitutes a first step towards modelling from first principles potentially observable stratified MRI effects in low-luminosity accretion discs around black holes.
Discovering DNA shape motifs with multiple DNA shape features: generalization, methods, and validation
Authors: Chen Nanjun , Yu Jixiang , Liu Zhe , Meng Lingkuan , Li Xiangtao , Wong Ka-Chun
Published: April 2024

DNA motifs are crucial patterns in gene regulation. DNA-binding proteins (DBPs), including transcription factors, can bind to specific DNA motifs to regulate gene expression and other cellular activities. Past studies suggest that DNA shape features could be subtly involved in DNA–DBP interactions. Therefore, the shape motif annotations based on intrinsic DNA topology can deepen the understanding of DNA–DBP binding. Nevertheless, high-throughput tools for DNA shape motif discovery that incorporate multiple features altogether remain insufficient. To address it, we propose a series of methods to discover non-redundant DNA shape motifs with the generalization to multiple motifs in multiple shape features. Specifically, an existing Gibbs sampling method is generalized to multiple DNA motif discovery with multiple shape features. Meanwhile, an expectation-maximization (EM) method and a hybrid method coupling EM with Gibbs sampling are proposed and developed with promising performance, convergence capability, and efficiency. The discovered DNA shape motif instances reveal insights into low-signal ChIP-seq peak summits, complementing the existing sequence motif discovery works. Additionally, our modelling captures the potential interplays across multiple DNA shape features. We provide a valuable platform of tools for DNA shape motif discovery. An R package is built for open accessibility and long-lasting impact: https://zenodo.org/doi/10.5281/zenodo.10558980.
Fine-tuning the tRNA anticodon arm for multiple/consecutive incorporations of β-amino acids and analogs
Authors: Katoh Takayuki , Suga Hiroaki
Published: April 2024

Ribosomal incorporation of β-amino acids into nascent peptides is much less efficient than that of the canonical α-amino acids. To overcome this, we have engineered a tRNA chimera bearing T-stem of tRNAGlu and D-arm of tRNAPro1, referred to as tRNAPro1E2, which efficiently recruits EF-Tu and EF-P. Using tRNAPro1E2 indeed improved β-amino acid incorporation. However, multiple/consecutive incorporations of β-amino acids are still detrimentally poor. Here, we attempted fine-tuning of the anticodon arm of tRNAPro1E2 aiming at further enhancement of β-amino acid incorporation. By screening various mutations introduced into tRNAPro1E2, C31G39/C28G42 mutation showed an approximately 3-fold enhancement of two consecutive incorporation of β-homophenylglycine (βPhg) at CCG codons. The use of this tRNA made it possible for the first time to elongate up to ten consecutive βPhg's. Since the enhancement effect of anticodon arm mutations differs depending on the codon used for β-amino acid incorporation, we optimized anticodon arm sequences for five codons (CCG, CAU, CAG, ACU and UGG). Combination of the five optimal tRNAs for these codons made it possible to introduce five different kinds of β-amino acids and analogs simultaneously into model peptides, including a macrocyclic scaffold. This strategy would enable ribosomal synthesis of libraries of macrocyclic peptides containing multiple β-amino acids.
Bridging DNA contacts allow Dps from E. coli to condense DNA
Authors: Shahu Sneha , Vtyurina Natalia , Das Moumita , Meyer Anne S , Ganji Mahipal , Abbondanzieri Elio A
Published: April 2024

The DNA-binding protein from starved cells (Dps) plays a crucial role in maintaining bacterial cell viability during periods of stress. Dps is a nucleoid-associated protein that interacts with DNA to create biomolecular condensates in live bacteria. Purified Dps protein can also rapidly form large complexes when combined with DNA in vitro. However, the mechanism that allows these complexes to nucleate on DNA remains unclear. Here, we examine how DNA topology influences the formation of Dps–DNA complexes. We find that DNA supercoils offer the most preferred template for the nucleation of condensed Dps structures. More generally, bridging contacts between different regions of DNA can facilitate the nucleation of condensed Dps structures. In contrast, Dps shows little affinity for stretched linear DNA before it is relaxed. Once DNA is condensed, Dps forms a stable complex that can form inter-strand contacts with nearby DNA, even without free Dps present in solution. Taken together, our results establish the important role played by bridging contacts between DNA strands in nucleating and stabilizing Dps complexes.
SingmiR: a single-cell miRNA alignment and analysis tool
Authors: Engel Annika , Rishik Shusruto , Hirsch Pascal , Keller Verena , Fehlmann Tobias , Kern Fabian , Keller Andreas
Published: April 2024

Single-cell RNA sequencing (RNA-seq) has revolutionized our understanding of cell biology, developmental and pathophysiological molecular processes, paving the way toward novel diagnostic and therapeutic approaches. However, most of the gene regulatory processes on the single-cell level are still unknown, including post-transcriptional control conferred by microRNAs (miRNAs). Like the established single-cell gene expression analysis, advanced computational expertise is required to comprehensively process newly emerging single-cell miRNA-seq datasets. A web server providing a workflow tailored for single-cell miRNA-seq data with a self-explanatory interface is currently not available. Here, we present SingmiR, enabling the rapid (pre-)processing and quantification of human miRNAs from noncoding single-cell samples. It performs read trimming for different library preparation protocols, generates automated quality control reports and provides feature-normalized count files. Numerous standard and advanced analyses such as dimension reduction, clustered feature heatmaps, sample correlation heatmaps and differential expression statistics are implemented. We aim to speed up the prototyping pipeline for biologists developing single-cell miRNA-seq protocols on small to medium-sized datasets. SingmiR is freely available to all users without the need for a login at https://www.ccb.uni-saarland.de/singmir.
ADMETlab 3.0: an updated comprehensive online ADMET prediction platform enhanced with broader coverage, improved performance, API functionality and decision support
Authors: Fu Li , Shi Shaohua , Yi Jiacai , Wang Ningning , He Yuanhang , Wu Zhenxing , Peng Jinfu , Deng Youchao , Wang Wenxuan , Wu Chengkun , Lyu Aiping , Zeng Xiangxiang , Zhao Wentao , Hou Tingjun , Cao Dongsheng
Published: April 2024

ADMETlab 3.0 is the second updated version of the web server that provides a comprehensive and efficient platform for evaluating ADMET-related parameters as well as physicochemical properties and medicinal chemistry characteristics involved in the drug discovery process. This new release addresses the limitations of the previous version and offers broader coverage, improved performance, API functionality, and decision support. For supporting data and endpoints, this version includes 119 features, an increase of 31 compared to the previous version. The updated number of entries is 1.5 times larger than the previous version with over 400 000 entries. ADMETlab 3.0 incorporates a multi-task DMPNN architecture coupled with molecular descriptors, a method that not only guaranteed calculation speed for each endpoint simultaneously, but also achieved a superior performance in terms of accuracy and robustness. In addition, an API has been introduced to meet the growing demand for programmatic access to large amounts of data in ADMETlab 3.0. Moreover, this version includes uncertainty estimates in the prediction results, aiding in the confident selection of candidate compounds for further studies and experiments. ADMETlab 3.0 is publicly for access without the need for registration at: https://admetlab3.scbdd.com.
Hypoxia-inducible factor prolyl hydroxylase inhibitors for anaemia in chronic kidney disease: a clinical practice document by the European Renal Best Practice board of the European Renal Association
Authors: Stoumpos Sokratis , Crowe Kirsty , Sarafidis Pantelis , Barratt Jonathan , Bolignano Davide , Del Vecchio Lucia , Małyszko Jolanta , Więcek Andrzej , Ortiz Alberto , Cozzolino Mario
Published: April 2024

Anaemia is a common complication of chronic kidney disease (CKD) and is associated with poor long-term outcomes and quality of life. The use of supplemental iron, erythropoiesis-stimulating agents (ESAs) and blood transfusions has been the mainstay for treatment of anaemia in CKD for more than 3 decades. Despite available treatments, CKD patients with anaemia are undertreated and moderate–severe anaemia remains prevalent in the CKD population. Anaemia has consistently been associated with greater mortality, hospitalization, cardiovascular events and CKD progression in CKD patients, and the risk increases with anaemia severity.

Hypoxia-inducible factor (HIF) prolyl hydroxylase (PH) inhibitors have a novel mechanism of action by mimicking the body's response to hypoxia and have emerged as an alternative to ESAs for treatment of anaemia in CKD. Their efficacy in correcting and maintaining haemoglobin has been demonstrated in >30 phase 3 clinical trials. Additionally, HIF activation results in various pleiotropic effects beyond erythropoiesis, with cholesterol reduction and improved iron homeostasis and potential anti-inflammatory effects. The long-term safety of these agents, particularly with respect to cardiovascular and thromboembolic events, and their possible effect on tumour growth needs to be fully elucidated. This article presents in detail the effects of HIF-PH inhibitors, describes their mechanisms of action and pharmacologic properties and discusses their place in the treatment of anaemia in CKD according to the available evidence.
Better kidney allograft survival despite higher-risk donor and recipient characteristics between 1995 and 2014
Authors: Ng Monica Suet Ying , Jones Andrew Thomas , Mallett Andrew John , O'Shaughnessy Michelle Marie
Published: April 2024

Background and hypothesis

Advances in organ procurement, surgical techniques, immunosuppression regimens, and prophylactic antibiotic therapies have dramatically improved kidney transplant graft failure. It is unclear how these interventions have affected longer-term graft failure. It is hypothesized that graft failure has improved over the last 20 years.

Methods

Data on all first kidney transplants from 1995 to 2014 were extracted from the Australia and New Zealand Dialysis and Transplant Registry with follow-up as of 31 December 2021. Primary exposure was transplant era, classified into 5-year intervals. Primary outcome was all-cause 5-year graft failure. Secondary outcomes included all-cause 10-year graft failure and cause-specific graft failure. Kaplan–Meier curves and multivariable Cox proportional hazards regression models were used to assess trends in all-cause graft failure. Fine–Gray subdistribution hazard models verified that changes in death rates were not biasing the Cox proportional hazards regression models. Cumulative incidence functions were used to assess temporal trends in cause-specific graft failure.

Results

Across 10 871 kidney transplants, there was a shift towards transplanting more recipients aged >45 years old, with more comorbidities, longer dialysis vintage, body mass index >30 kg/m2, and greater human leukocyte antigen mismatches. Donor age has increased but no clear shift in donor source was observed. Compared to 1995–99 (reference), the adjusted hazard ratio for 5-year graft failure was 0.78 (95% CI 0.67–0.91), 0.70 (95% CI 0.59–0.83), and 0.60 (95% CI 0.50–0.73) for 2000–04, 2005–09, and 2010–14, respectively. Ten-year graft failure similarly reduced from 0.83 (95% CI 0.74–0.93) for 2000–04 to 0.78 (95% CI 0.68–0.89) for 2010–14, compared to 1995–99.

Conclusion

Medium- and long-term all-cause graft failure has improved steadily since 1995–99. Significant reductions in graft failure due to rejection and vascular causes were observed at 5 years, and due to rejection, vascular causes, death, and glomerular disease at 10 years.