bluuebunny/crossref_metadata_2025 huggingface dataset:
The role and mechanism of Bacillus megaterium strain A14 in inhibiting the cadmium uptake by peanut plants in acidic red soil
Authors: Yao Xiangzhi , Ren Jingyu , Fang Lirong , Sun Kai , He Wei
Published: May 2024

Aims

This study explores the potential of cadmium (Cd)-resistant bacteria, specifically Bacillus megaterium A14, to decrease Cd accumulation in peanuts, a crop susceptible to metal uptake from contaminated soils, by understanding the bacterium’s impact on plant Cd absorption mechanisms.

Methods and Results

Through pot experiments, we observed that A14 inoculation significantly increased peanut biomass under Cd stress conditions, primarily by immobilizing the metal and reducing its bioavailability. The bacterium effectively changed the distribution of Cd, with a notable 46.53% reduction in the exchangeable fraction, which in turn limited the expression of genes related to Cd transport in peanuts. Additionally, A14 enhanced the plant’s antioxidant response, improving its tolerance to stress. Microbial analysis through 16S sequencing demonstrated that A14 inoculation altered the peanut rhizosphere, particularly by increasing populations of Firmicutes and Proteobacteria, which play crucial roles in soil remediation from heavy metals.

Conclusion

The A14 strain effectively counters Cd toxicity in peanuts, promoting growth through soil Cd sequestration, root barrier biofilm formation, antioxidant system enhancement, suppression of Cd transport genes, and facilitation of Cd-remediating microorganisms.
The role of mechanotransduction in tendon
Authors: Nakamichi Ryo , Asahara Hiroshi
Published: May 2024

Tendons play an important role in the maintenance of motor function by connecting muscles and bones and transmitting forces. Particularly, the role of mechanical stress has primarily focused on the key mechanism of tendon homeostasis, with much research on this topic. With the recent development of molecular biological techniques, the mechanisms of mechanical stress sensing and signal transduction have been gradually elucidated with the identification of mechanosensor in tendon cells and the master regulator in tendon development. This review provides a comprehensive overview of the structure and function of tendon tissue, including the role for physical performance and the detailed mechanism of mechanotransduction in its regulation. An important lesson is that the role of mechanotransduction in tendon tissue is only partially clarified, indicating the complexity of the mechanisms of motor function and fueling increasing interest in uncovering these mechanisms.
Numerical simulation of acoustic wave propagation by finite element method based on optimized matrices
Authors: Li Lei , Wen Xiaotao , Tang Chao , Zhou Dongyong , Zhang Songgen
Published: May 2024

Based on the wave equation, scholars worldwide have proposed various methods for numerical simulation of seismic wave propagation in underground and surface media. The finite element method offers a unique advantage in accurately depicting the undulating surfaces and steep palaeoburial hills with its triangular mesh. However, its computational efficiency cannot meet our needs while lots of memory is occupied. To address this, we optimized and improved the critical mass matrix and stiffness matrix of spatial discretization of the acoustic wave equation. We first fully utilized the flexibility of triangles to fit different undulating terrains, then reorganized the numbering of triangle mesh nodes and elements to reduce the bandwidth of the matrices, and then used optimized matrices for solving. The Crank–Nicolson scheme was adopted for time discretization, and the perfectly matched layer condition was utilized to eliminate false waves reflected from the boundary. The numerical experiments with simple and significant fluctuation models proved that this method can accelerate computational efficiency while ensuring computational accuracy.
Combination of fuzzy control and reinforcement learning for wind turbine pitch control
Authors: Sierra-Garcia J Enrique , Santos Matilde
Published: May 2024

The generation of the pitch control signal in a wind turbine (WT) is not straightforward due to the nonlinear dynamics of the system and the coupling of its internal variables; in addition, they are subjected to the uncertainty that comes from the random nature of the wind. Fuzzy logic has proved useful in applications with changing system parameters or where uncertainty is relevant as in this one, but the tuning of the fuzzy logic controller (FLC) parameters is neither straightforward nor an easy task. On the other hand, reinforcement learning (RL) allows systems to automatically learn, and this capability can be exploited to tune the FLC. In this work, a WT pitch control architecture that uses RL to tune the membership functions and scale the output of a fuzzy controller is proposed. The RL strategy calculates the fuzzy controller gains in order to reduce the output power error of the WT according to the wind speed. Different reward mechanisms based on the output power error have been considered. Simulation results with different wind profiles show that this architecture performs better (123.7 W) in terms of power errors than an FLC without RL (133.2 W) or a simpler PID (208.8 W). Even more, it provides a smooth response and outperforms other hybrid controllers such as RL-PID and radial basis function neural network control.
Płonka adjunction
Authors: Climent Vidal J , Cosme Llópez E
Published: May 2024

Let $\varSigma $ be a signature without $0$-ary operation symbols and $\textsf{Sl}$ the category of semilattices. Then, after defining and investigating the categories $\int ^{\textsf{Sl}}\textrm{Isys}_{\varSigma }$, of inductive systems of $\varSigma $-algebras over all semilattices, which are ordered pairs $\boldsymbol{\mathscr{A}}= (\textbf{I},\mathscr{A})$ where $\textbf{I}$ is a semilattice and $\mathscr{A}$ an inductive system of $\varSigma $-algebras relative to $\textbf{I}$, and PłAlg$(\varSigma )$, of Płonka $\varSigma $-algebras, which are ordered pairs $(\textbf{A},D)$ where $\textbf{A}$ is a $\varSigma $-algebra and $D$ a Płonka operator for $\textbf{A}$, i.e. in the traditional terminology, a partition function for $\textbf{A}$, we prove the main result of the paper: There exists an adjunction, which we call the Płonka adjunction, from $\int ^{\textsf{Sl}}\textrm{Isys}_{\varSigma }$ to PłAlg$(\varSigma )$.
A new species of the endemic Tarsomys clade (Muridae, Rodentia) from eastern Mindanao Island, Philippines
Authors: Rickart Eric A , Rowsey Dakota M , Ibañez Jayson C , Quidlat Roselyn S , Balete Danilo S , Heaney Lawrence R
Published: May 2024

Based on molecular and morphological evidence, we describe a new species of murine rodent from Mt. Kampalili in easternmost Mindanao Island, Philippines. It is the third known species of Tarsomys, a genus endemic to Mindanao. The new species differs from congeners (T. apoensis and T. echinatus) in having smaller body size, shorter tail, smaller hind feet, soft and dense pelage of darker color, smaller skull with a broader zygomatic plate, shorter incisive foramina, and longer auditory bullae. The new species belongs to the “Tarsomys clade” of tribe Rattini that has diversified principally on Mindanao where, in addition to the 3 species of Tarsomys, it is represented by 2 species of Limnomys and 1 species of Baletemys. The Tarsomys clade also includes the Rattus everetti complex which is widespread throughout the oceanic portion of the Philippines and likely consists of at least 4 species. Molecular phylogenetic analysis strongly supports a sister relationship between this new species and T. apoensis, which diverged approximately 1.0 to 1.75 Ma. The phylogenetic position, morphological distinctness, and relatively ancient persistence of this species support within-island diversification as the most substantial contributor to existing species richness of small mammals in the Philippines.
A review ofMusca sorbens(Diptera: Muscidae) andMusca domesticabehavior and responses to chemical and visual cues
Authors: Jones Robert T , Fagbohun Ifeoluwa K , Spencer Freya I , Chen-Hussey Vanessa , Paris Laura A , Logan James G , Hiscox Alexandra
Published: May 2024

Musca flies (Diptera: Muscidae) have been found culpable in the mechanical transmission of several infectious agents, including viruses, bacteria, protozoans, and helminths, particularly in low-income settings in tropical regions. In large numbers, these flies can negatively impact the health of communities and their livestock through the transmission of pathogens. In some parts of the world, Musca sorbens is of particular importance because it has been linked with the transmission of trachoma, a leading cause of preventable and irreversible blindness or visual impairment caused by Chlamydia trachomatis, but the contribution these flies make to trachoma transmission has not been quantified and even less is known for other pathogens. Current tools for control and monitoring of house flies remain fairly rudimentary and have focused on the use of environmental management, insecticides, traps, and sticky papers. Given that the behaviors of flies are triggered by chemical cues from their environment, monitoring approaches may be improved by focusing on those activities that are associated with nuisance behaviors or with potential pathogen transmission, and there are opportunities to improve fly control by exploiting behaviors toward semiochemicals that act as attractants or repellents. We review current knowledge on the odor and visual cues that affect the behavior of M. sorbens and Musca domestica, with the aim of better understanding how these can be exploited to support disease monitoring and guide the development of more effective control strategies.
Wire-tracking of bent electric cable using X-ray CT and deep active learning
Authors: Hoshina Yutaka , Yamamoto Takuma , Uemura Shigeaki
Published: May 2024

We have demonstrated a quantification of all component wires in a bent electric cable, which is necessary for discussion of cable products in actual use cases. Quantification became possible for the first time because of our new technologies for image analysis of bent cables. In this paper, various image analysis techniques to detect all wire tracks in a bent cable are demonstrated. Unique cross-sectional image construction and deep active learning schemes are the most important items in this study. These methods allow us to know the actual state of cables under external loads, which makes it possible to elucidate the mechanisms of various phenomena related to cables in the field and further improve the quality of cable products.
Beyond floral initiation: the role of flower bud dormancy in flowering time control of annual plants
Authors: Penfield Steven
Published: May 2024

The phenology of temperate perennials, including the timing of vegetative growth and flowering, is well known to be controlled by seasonal dormancy cycles. Dormant structures are known as buds and have specialized covering structures, symplastic isolation from the plant, and often autonomous stores of carbon and nitrogen reserves. In contrast, in annual plants, our current understanding of the control of the timing of flowering focuses on the mechanisms affecting floral initiation, the transition from a vegetative apical meristem to a inflorescence meristem producing flower primordia in place of leaves. Recently we revealed that annual crops in Brassicaceae exhibit chilling-responsive growth control in a manner closely resembling bud dormancy breakage in perennial species. Here I discuss evidence that vernalization in autumn is widespread and further discuss its role in inducing flower bud set prior to winter. I also review evidence that flower bud dormancy has a more widespread role in annual plant flowering time control than previously appreciated.
Exploring natural genetic diversity in a bread wheat multi-founder population: dual imaging of photosynthesis and stomatal kinetics
Authors: Faralli Michele , Mellers Greg , Wall Shellie , Vialet-Chabrand Silvere , Forget Guillaume , Galle Alexander , Van Rie Jeron , Gardner Keith A , Ober Eric S , Cockram James , Lawson Tracy
Published: May 2024

Recent research has shown that optimizing photosynthetic and stomatal traits holds promise for improved crop performance. However, standard phenotyping tools such as gas exchange systems have limited throughput. In this work, a novel approach based on a bespoke gas exchange chamber allowing combined measurement of the quantum yield of PSII (Fq'/Fm'), with an estimation of stomatal conductance via thermal imaging was used to phenotype a range of bread wheat (Triticum aestivum L.) genotypes. Using the dual-imaging methods and traditional approaches, we found broad and significant variation in key traits, including photosynthetic CO2 uptake at saturating light and ambient CO2 concentration (Asat), photosynthetic CO2 uptake at saturating light and elevated CO2 concentration (Amax), the maximum velocity of Rubisco for carboxylation (Vcmax), time for stomatal opening (Ki), and leaf evaporative cooling. Anatomical analysis revealed significant variation in flag leaf adaxial stomatal density. Associations between traits highlighted significant relationships between leaf evaporative cooling, leaf stomatal conductance, and Fq'/Fm', highlighting the importance of stomatal conductance and stomatal rapidity in maintaining optimal leaf temperature for photosynthesis in wheat. Additionally, gsmin and gsmax were positively associated, indicating that potential combinations of preferable traits (i.e. inherently high gsmax, low Ki, and maintained leaf evaporative cooling) are present in wheat. This work highlights the effectiveness of thermal imaging in screening dynamic gs in a panel of wheat genotypes. The wide phenotypic variation observed suggested the presence of exploitable genetic variability in bread wheat for dynamic stomatal conductance traits and photosynthetic capacity for targeted optimization within future breeding programmes.
Turmeric and curcumin as adjuncts in controlling Helicobacter pylori-associated diseases: a narrative review
Authors: Boyanova Lyudmila , Medeiros José , Yordanov Daniel , Gergova Raina , Markovska Rumyana
Published: May 2024

Non-antibiotic adjuncts may improve Helicobacter pylori infection control. Our aim was to emphasize curcumin benefits in controlling H. pylori infection. We discussed publications in English mostly published since 2020 using keyword search. Curcumin is the main bioactive substance in turmeric. Curcumin inhibited H. pylori growth, urease activity, three cag genes, and biofilms through dose- and strain-dependent activities. Curcumin also displayed numerous anticancer activities such as apoptosis induction, anti-inflammatory and anti-angiogenic effects, caspase-3 upregulation, Bax protein enhancement, p53 gene activation, and chemosensitization. Supplementing triple regimens, the agent increased H. pylori eradication success in three Iranian studies. Bioavailability was improved by liposomal preparations, lipid conjugates, electrospray-encapsulation, and nano-complexation with proteins. The agent was safe at doses of 0.5–>4 g daily, the most common (in 16% of the users) adverse effect being gastrointestinal upset. Notably, curcumin favorably influences the intestinal microbiota and inhibits Clostridioides difficile. Previous reports showed the inhibitory effect of curcumin on H pylori growth. Curcumin may become an additive in the therapy of H. pylori infection, an adjunct for gastric cancer control, and an agent beneficial to the intestinal microbiota. Further examination is necessary to determine its optimal dosage, synergy with antibiotics, supplementation to various eradication regimens, and prophylactic potential.
The thesan project: connecting ionized bubble sizes to their local environments during the Epoch of Reionization
Authors: Neyer Meredith , Smith Aaron , Kannan Rahul , Vogelsberger Mark , Garaldi Enrico , Galárraga-Espinosa Daniela , Borrow Josh , Hernquist Lars , Pakmor Rüdiger , Springel Volker
Published: May 2024

An important characteristic of cosmic hydrogen reionization is the growth of ionized gas bubbles surrounding early luminous objects. Ionized bubble sizes are beginning to be probed using Lyman α emission from high-redshift galaxies, and will also be probed by upcoming 21 cm maps. We present results from a study of bubble sizes using the state-of-the-art thesan radiation-hydrodynamics simulation suite, which self-consistently models radiation transport and realistic galaxy formation. We employ the mean free path method and track the evolution of the effective ionized bubble size at each point (Reff) throughout the Epoch of Reionization. We show that there is a slow growth period for regions ionized early, but a rapid ‘flash ionization’ process for regions ionized later as they immediately enter a large, pre-existing bubble. We also find that bright sources are preferentially in larger bubbles, and find consistency with recent observational constraints at z ≳ 9, but tension with idealized Lyman α damping-wing models at z ≈ 7. We find that high-overdensity regions have larger characteristic bubble sizes, but the correlation decreases as reionization progresses, likely due to runaway formation of large percolated bubbles. Finally, we compare the redshift at which a region transitions from neutral to ionized (zreion) with the time it takes to reach a given bubble size and conclude that zreion is a reasonable local probe of small-scale bubble size statistics ($R_\text{eff} \lesssim 1\, \rm {cMpc}$). However, for larger bubbles, the correspondence between zreion and size statistics weakens due to the time delay between the onset of reionization and the expansion of large bubbles, particularly at high redshifts.
Unveiling the complex circumgalactic medium: a comparative study of merging and non-interacting galaxy groups
Authors: Fernández-Figueroa Antonia , Kacprzak Glenn G , Nielsen Nikole M , Barone Tania M , Nateghi Hasti , Sameer  , Fisher Deanne B , Chu Bronwyn Reichardt
Published: May 2024

While most galaxies live in group environments where they undergo an accelerated evolution, the characteristics of their circumgalactic medium (CGM) remain uncertain. We present an analysis of the CGM of two galaxy groups in different stages of interaction: (G1) a close pair of galaxies (z = 0.043) separated by 87 kpc that do not show signs of interactions and (G2) four merging galaxies (z = 0.098) separated by 10 kpc. We present spatially resolved Keck/Keck Cosmic Web Imager galaxy observations and Hubble Space Telescope (HST)/COS quasar spectra (G1 at 48 kpc and G2 at 100 kpc away) to quantify both the resolved galaxy and CGM properties in these two different group environments. G1 contains two typical star-forming galaxies with no evidence of strong outflows. G2 contains two star-forming, one post-starburst and one quiescent galaxy. Both groups have a range of CGM-detected metal lines (H i, C ii, Si ii, Si iii, N v, and O vi). Despite G2 being twice as far from the quasar, G2 has $\log (N({{{\rm H}{\small I}}})/{\rm cm}^{-2})=17.33$, compared to $\log (N({{{\rm H}{\small I}}})/{\rm cm}^{-2})=16.43$ for G1. We find that the CGM of the merging galaxies (G2) is more kinematically complex, is in a higher ionization state, spans a wider range of metallicities and column densities, has smaller cloud sizes, and is inconsistent with the simple superposition model that seems to match well with G1. We conclude that the complexity of the CGM in merging galaxies surpasses that of not strongly interacting galaxies, suggesting that mergers play a significant role in shaping the intricate structure of the CGM.
Multiwavelength photometric study of RR lyrae variables in the globular cluster NGC 5272 (Messier 3)
Authors: Kumar Nitesh , Bhardwaj Anupam , Singh Harinder P , Rejkuba Marina , Marconi Marcella , Prugniel Philippe
Published: May 2024

We present a comprehensive photometric study of RR Lyrae stars in the M3 globular cluster, utilizing a vast data set of 3140 optical (UBVRI) CCD images spanning 35 yr from astronomical data archives. We have successfully identified previously known 238 RR Lyrae stars from the photometric data, comprising 178 RRab, 49 RRc, and 11 RRd stars. Multiband periodogram was used to significantly improve the long-term periods of 65 per cent of RR Lyrae stars in our sample, thanks to the unprecedentedly long temporal coverage of the observations. The light curve templates were used to obtain accurate and precise mean magnitudes and amplitudes of all RR Lyrae variables. We combined optical (UBVRI) and near-infrared (NIR, JHKs) photometry of RR Lyrae variables to investigate their location in the colour-magnitude diagrams as well as the pulsation properties such as period distributions, Bailey diagrams and amplitude ratios. The period–luminosity relations in R and I bands and Period–Wesenheit relations were derived after excluding outliers identified in CMDs. The Period–Wesenheit relations calibrated via the theoretically predicted relations were used to determine a distance modulus of $\mu = 15.04 \pm 0.04 \, {\rm (stats)} \pm 0.19 \, {\rm {(syst.)}}$ mag (using metal-independent WBV Wesenheit) and $\mu = 15.03 \pm 0.04 \, {\rm (stats)} \pm 0.17 \, {\rm {(syst.)}}$ mag (using metal-dependent WVI Wesenheit). Our distance measurements are in excellent agreement with published distances to M3 in the literature. We also employed an artificial neural network based comparison of theoretical and observed light curves to determine physical parameters (mass, luminosity, and effective temperature) for 79 non-Blazhko RRab stars that agree with limited literature measurements.
TOI-837 b is a young Saturn-sized exoplanet with a massive 70 M⊕ core
Authors: Barragán Oscar , Yu Haochuan , Freckelton Alix Violet , Meech Annabella , Cretignier Michael , Mortier Annelies , Aigrain Suzanne , Klein Baptiste , O’Sullivan Niamh K , Gillen Edward , Nielsen Louise Dyregaard , Mallorquín Manuel , Zicher Norbert
Published: May 2024

We present an exhaustive photometric and spectroscopic analysis of TOI-837, a F9/G0 35 Myr young star, hosting a transiting exoplanet, TOI-837 b, with an orbital period of ∼8.32 d. Utilizing data from the Transiting Exoplanet Survey Satellite and ground-based observations, we determine a planetary radius of $0.818_{-0.024}^{+0.034}$ RJ for TOI-837 b. Through detailed High Accuracy Radial Velocity Planet Searcher spectroscopic time series analysis, we derive a Doppler semi-amplitude of $34.7_{-5.6}^{+5.3}$ ${\rm m\, s^{-1}}$, corresponding to a planetary mass of $0.379_{-0.061}^{+0.058}$ MJ. The derived planetary properties suggest a substantial core of approximately 70 M⊕, constituting about 60 per cent of the planet’s total mass. This finding poses a significant challenge to existing theoretical models of core formation. We propose that future atmospheric observations with JWST could provide insights into resolving ambiguities of TOI-837 b, offering new perspectives on its composition, formation, and evolution.
A semi-analytical model for the propagation of a relativistic jet in a magnetized medium
Authors: García-García Leonardo , López-Cámara Diego , Lazzati Davide
Published: May 2024

The merger of two magnetized compact objects, such as neutron stars, forms a compact object which may launch a relativistic and collimated jet. Numerical simulations of the process show that a dense and highly magnetized medium surrounds the system. This study presents a semi-analytical model that models the effects that a static magnetized medium with a tangled field produces in relativistic, collimated, and non-magnetized jets. The model is a first approximation that addresses the magnetic field present in the medium and is based on pressure equilibrium principles between the jet, cocoon, and external medium. A fraction of the ambient medium field is allowed to be entrained in the cocoon. We find that the jet and cocoon properties may be affected by high magnetic fields (≳ 1015 G) and mixing. The evolution of the system may vary up to $\sim 10{{\ \rm per\ cent}}$ (compared to the non-magnetized case). Low-mixing may produce a slower broader jet with a broader and more energetic cocoon would be produced. On the other hand, high-mixing could produce a faster narrower jet with a narrow and less-energetic cocoon. Two-dimensional hydrodynamical simulations are used to validate the model and to constrain the mixing parameter. Although the magnetic field and mixing have a limited effect, our semi-analytic model captures the general trend consistent with numerical results. For high magnetization, the results were found to be more consistent with the low mixing case in our semi-analytic model.
H i galaxy signatures in the SARAO MeerKAT galactic plane survey − III. Unveiling the obscured part of the Vela Supercluster
Authors: Rajohnson Sambatriniaina H A , Kraan-Korteweg Renée C , Chen Hao , Frank Bradley S , Steyn Nadia , Kurapati Sushma , Pisano D J , Staveley-Smith Lister , Serra Paolo , Goedhart Sharmila , Camilo Fernando
Published: May 2024

We conducted a search for $\textrm {H}\, \scriptstyle \mathrm{I}$ emission of the gas-rich galaxies in the Vela region (260° ≤ ℓ ≤ 290°, −2° ≤ b ≤ 1°) to explore the Vela Supercluster (VSCL) at Vhel ∼ 18 000 $\rm km\, s^{-1}$, largely obscured by Galactic dust. Within the mostly Radio Frequency Interference-free band (250 < Vhel < 25 000 $\rm km\, s^{-1}$) of MeerKAT, the analysis focuses on 157 hexagonally distributed pointings extracted from the South African Radio Astronomy Observatory MeerKAT Galactic Plane Survey located in the Vela region (Vela−SMGPS). These were combined into 10 contiguous mosaics, covering an ∼90 square degrees area. Among the 843 $\textrm {H}\, \scriptstyle \mathrm{I}$ detected sources, 39 were previously discovered in the H i Parkes Zone of Avoidance survey (Vhel < 12 000 $\rm km\, s^{-1}$; rms ∼ 6 $\rm mJy\, beam^{-1}$). With the improved rms level of the Vela−SMGPS, i.e. 0.29–0.56 $\rm mJy\, beam^{-1}$, our study unveils nearly 12 times more detections (471 candidates) in that same velocity range. We furthermore could identify 187 galaxy candidates with an $\textrm {H}\, \scriptstyle \mathrm{I}$ mass limit reaching $\log (M_{\rm HI}/\rm {\rm M}_{\odot }) = 9.44$ in the VSCL velocity range Vhel ∼ 19 500 ± 3500 $\rm km\, s^{-1}$. We find indications of two wall-like overdensities that confirm the original suspicion that these walls intersect at low latitudes around longitudes of ℓ ∼ 272°–278°. We also find a strong signature most likely associated with the Hydra/Antlia extension and evidence of a previously unknown narrow filament at Vhel ∼ 12 000 $\rm km\, s^{-1}$. This paper demonstrates the efficiency of systematic $\textrm {H}\, \scriptstyle \mathrm{I}$ surveys with the Square Kilometre Array (SKA) precursor MeerKAT, even in the most obscured part of the Zone of Avoidance.
AlPaCas: allele-specific CRISPR gene editing through a protospacer-adjacent-motif (PAM) approach
Authors: Rosignoli Serena , Lustrino Elisa , Conci Alessio , Fabrizi Alessandra , Rinaldo Serena , Latella Maria Carmela , Enzo Elena , Prosseda Gianni , De Rosa Laura , De Luca Michele , Paiardini Alessandro
Published: May 2024

Gene therapy of dominantly inherited genetic diseases requires either the selective disruption of the mutant allele or the editing of the specific mutation. The CRISPR-Cas system holds great potential for the genetic correction of single nucleotide variants (SNVs), including dominant mutations. However, distinguishing between single-nucleotide variations in a pathogenic genomic context remains challenging. The presence of a PAM in the disease-causing allele can guide its precise targeting, preserving the functionality of the wild-type allele. The AlPaCas (Aligning Patients to Cas) webserver is an automated pipeline for sequence-based identification and structural analysis of SNV-derived PAMs that satisfy this demand. When provided with a gene/SNV input, AlPaCas can: (i) identify SNV-derived PAMs; (ii) provide a list of available Cas enzymes recognizing the SNV (s); (iii) propose mutational Cas-engineering to enhance the selectivity towards the SNV-derived PAM. With its ability to identify allele-specific genetic variants that can be targeted using already available or engineered Cas enzymes, AlPaCas is at the forefront of advancements in genome editing. AlPaCas is open to all users without a login requirement and is freely available at https://schubert.bio.uniroma1.it/alpacas.
ViralFlow v1.0—a computational workflow for streamlining viral genomic surveillance
Authors: da Silva Alexandre Freitas , da Silva Neto Antonio Marinho , Aksenen Cleber Furtado , Jeronimo Pedro Miguel Carneiro , Dezordi Filipe Zimmer , Almeida Suzana Porto , Costa Hudson Marques Paula , Salvato Richard Steiner , Campos Tulio de Lima , Wallau Gabriel da Luz , of the Fiocruz Genomic Network on behalf
Published: May 2024

ViralFlow v1.0 is a computational workflow developed for viral genomic surveillance. Several key changes turned ViralFlow into a general-purpose reference-based genome assembler for all viruses with an available reference genome. New virus-agnostic modules were implemented to further study nucleotide and amino acid mutations. ViralFlow v1.0 runs on a broad range of computational infrastructures, from laptop computers to high-performance computing (HPC) environments, and generates standard and well-formatted outputs suited for both public health reporting and scientific problem-solving. ViralFlow v1.0 is available at: https://viralflow.github.io/index-en.html.
A single-cell strategy for the identification of intronic variants related to mis-splicing in pancreatic cancer
Authors: Duman Emre Taylan , Sitte Maren , Conrads Karly , Mackay Adi , Ludewig Fabian , Ströbel Philipp , Ellenrieder Volker , Hessmann Elisabeth , Papantonis Argyris , Salinas Gabriela
Published: May 2024

Most clinical diagnostic and genomic research setups focus almost exclusively on coding regions and essential splice sites, thereby overlooking other non-coding variants. As a result, intronic variants that can promote mis-splicing events across a range of diseases, including cancer, are yet to be systematically investigated. Such investigations would require both genomic and transcriptomic data, but there currently exist very few datasets that satisfy these requirements. We address this by developing a single-nucleus full-length RNA-sequencing approach that allows for the detection of potentially pathogenic intronic variants. We exemplify the potency of our approach by applying pancreatic cancer tumor and tumor-derived specimens and linking intronic variants to splicing dysregulation. We specifically find that prominent intron retention and pseudo-exon activation events are shared by the tumors and affect genes encoding key transcriptional regulators. Our work paves the way for the assessment and exploitation of intronic mutations as powerful prognostic markers and potential therapeutic targets in cancer.
Structural dynamics of therapeutic nucleic acids with phosphorothioate backbone modifications
Authors: Carlesso Antonio , Hörberg Johanna , Deganutti Giuseppe , Reymer Anna , Matsson Pär
Published: May 2024

Antisense oligonucleotides (ASOs) offer ground-breaking possibilities for selective pharmacological intervention for any gene product-related disease. Therapeutic ASOs contain extensive chemical modifications that improve stability to enzymatic cleavage and modulate binding affinity relative to natural RNA/DNA. Molecular dynamics (MD) simulation can provide valuable insights into how such modifications affect ASO conformational sampling and target binding. However, force field parameters for chemically modified nucleic acids (NAs) are still underdeveloped. To bridge this gap, we developed parameters to allow simulations of ASOs with the widely applied phosphorothioate (PS) backbone modification, and validated these in extensive all-atom MD simulations of relevant PS-modified NA systems representing B-DNA, RNA, and DNA/RNA hybrid duplex structures. Compared to the corresponding natural NAs, single PS substitutions had marginal effects on the ordered DNA/RNA duplex, whereas substantial effects of phosphorothioation were observed in single-stranded RNA and B-DNA, corroborated by the experimentally derived structure data. We find that PS-modified NAs shift between high and low twist states, which could affect target recognition and protein interactions for phosphorothioated oligonucleotides. Furthermore, conformational sampling was markedly altered in the PS-modified ssRNA system compared to that of the natural oligonucleotide, indicating sequence-dependent effects on conformational preference that may in turn influence duplex formation.
PitViper: a software for comparative meta-analysis and annotation of functional screening data
Authors: Meslin Paul-Arthur , Kelly Lois M , Benbarche Salima , Lecourt Séverine , Lin Kevin H , Rutter Justine C , Bassil Christopher F , Itzykson Raphael , Wood Kris C , Puissant Alexandre , Lobry Camille
Published: May 2024

Recent advancements in shRNA and Cas protein technologies have enabled functional screening methods targeting genes or non-coding regions using single or pooled shRNA and sgRNA. CRISPR-based systems have also been developed for modulating DNA accessibility, resulting in CRISPR-mediated interference (CRISPRi) or activation (CRISPRa) of targeted genes or genomic DNA elements. However, there is still a lack of software tools for integrating diverse array of functional genomics screening outputs that could offer a cohesive framework for comprehensive data integration. Here, we developed PitViper, a flexible and interactive open-source software designed to fill this gap, providing reliable results for the type of elements being screened. It is an end-to-end automated and reproducible bioinformatics pipeline integrating gold-standard methods for functional screening analysis. Our sensitivity analyses demonstrate that PitViper is a useful tool for identifying potential super-enhancer liabilities in a leukemia cell line through genome-wide CRISPRi-based screening. It offers a robust, flexible, and interactive solution for integrating data analysis and reanalysis from functional screening methods, making it a valuable resource for researchers in the field.
Prophylactic treatment of FSGS recurrence in patients who relapsed on a previous kidney graft
Authors: Uro-Coste Charlotte , Lambert Céline , Audard Vincent , Couzi Lionel , Caillard Sophie , Büchler Matthias , Del Bello Arnaud , Malvezzi Paolo , Pernin Vincent , Colosio Charlotte , Mesnard Laurent , Bertrand Dominique , Martinez Frank , Ducloux Didier , Poulain Coralie , Thierry Antoine , Danthu Clément , Greze Clarisse , Lanaret Camille , Moal Valérie , Hertig Alexandre , Dantal Jacques , Legendre Christophe , Chatelet Valérie , Sicard Antoine , Gosset Clément , Maillard Nicolas , Duveau Agnès , Petit Clémence , Kamar Nassim , Heng Anne-Elisabeth , Anglicheau Dany , Garrouste Cyril
Published: May 2024

Background

Recurrence of focal segmental glomerulosclerosis (FSGS) is common after kidney transplantation and is classically associated with a significant decrease in graft survival. A major risk factor is a prior history of FSGS recurrence on a previous graft. This analysis reports the impact of a prophylactic treatment of FSGS recurrence in very high-risk patients who experienced a recurrence on a previous graft.

Methods

We performed a retrospective multicentre observational study in 25 French transplantation centres. The inclusion criteria were patients aged more than 18 years who had undergone kidney transplant between 31 December 2004 and 31 December 2020, and who had a history of FSGS recurrence on a previous graft.

Results

We identified 66 patients: 40 received prophylactic treatment (PT+), including intravenous cyclosporine and/or rituximab and/or plasmapheresis, and 26 did not receive any prophylactic treatment (PT–). The time to progression to end-stage kidney disease was similar between groups. The PT+ group was younger at FSGS diagnosis and at the time of kidney retransplantation and lost their previous graft faster. The overall recurrence rate was 72.7% (76.9% in the PT– group and 70.0% in the PT+ group, P = .54). At least partial remission was achieved in 87.5% of patients. The 5-year graft survival was 67.7% [95% confidence interval (CI) 53.4%–78.4%]: 65.1% (95% CI 48.7%–77.4%) in patients with FSGS recurrence vs 77.3% (95% CI 43.8%–92.3%) in patients without recurrence (P = .48).

Conclusion

Our study suggests that prophylactic treatment should not be used routinely in patients receiving a second transplantation after recurrence of FSGS on a previous graft. The recurrence rate is high regardless of the use of prophylactic treatment. However, the 5-year graft survival remains satisfactory.
Propionate and butyrate counteract renal damage and progression to chronic kidney disease
Authors: Corte-Iglesias Viviana , Saiz Maria Laura , Andrade-Lopez Ana Cristina , Salazar Nuria , Bernet Cristian Ruiz , Martin-Martin Cristina , Borra Jesús Martinez , Lozano Juan-Jose , Aransay Ana M , Diaz-Corte Carmen , Lopez-Larrea Carlos , Suarez-Alvarez Beatriz
Published: May 2024

Background

Short-chain fatty acids (SCFAs), mainly acetate, propionate and butyrate, are produced by gut microbiota through fermentation of complex carbohydrates that cannot be digested by the human host. They affect gut health and can contribute at the distal level to the pathophysiology of several diseases, including renal pathologies.

Methods

SCFA levels were measured in chronic kidney disease (CKD) patients (n = 54) at different stages of the disease, and associations with renal function and inflammation parameters were examined. The impact of propionate and butyrate in pathways triggered in tubular cells under inflammatory conditions was analysed using genome-wide expression assays. Finally, a pre-clinical mouse model of folic acid–induced transition from acute kidney injury to CKD was used to analyse the preventive and therapeutic potential of these microbial metabolites in the development of CKD.

Results

Faecal levels of propionate and butyrate in CKD patients gradually reduce as the disease progresses, and do so in close association with established clinical parameters for serum creatinine, blood urea nitrogen and the estimated glomerular filtration rate. Propionate and butyrate jointly downregulated the expression of 103 genes related to inflammatory processes and immune system activation triggered by tumour necrosis factor-α in tubular cells. In vivo, the administration of propionate and butyrate, either before or soon after injury, respectively, prevented and slowed the progression of damage. This was indicated by a decrease in renal injury markers, the expression of pro-inflammatory and pro-fibrotic markers, and recovery of renal function over the long term.

Conclusions

Propionate and butyrate levels are associated with a progressive loss of renal function in CKD patients. Early administration of these SCFAs prevents disease advancement in a pre-clinical model of acute renal damage, demonstrating their therapeutic potential independently of the gut microbiota.
Spillovers from tax shocks to the Euro area
Authors: Mierzwa Sascha
Published: May 2024

I study the spillover effects of legislated discretionary tax changes in the USA, Germany, and the UK to a panel of eleven Eurozone countries for the period 1980Q1–2018Q4 employing Local Projections. When considering aggregated tax shocks, I find little evidence for significant spillovers. When allowing for state-dependent effects, I find no effects of German or US tax cuts regardless of the state of the business cycle. When allowing for asymmetric effects, there is, in general, evidence for negative (positive) spillovers from US, German, and UK tax hikes (UK tax cuts). US tax hikes always cause adverse spillovers, whereas the effects for Germany and the UK are state dependent. When considering country-specific effects, the effects turn out as heterogeneous across the Eurozone countries. UK tax cuts are generally expansionary, whereas US (German) tax cuts cause positive spillovers mainly during recessionary (non-recessionary) times.
Who should decide how much information to collect?
Authors: Li Youping , Zhang Jianhu
Published: May 2024

This article examines the tradeoffs concerning the collection and disclosure of personal information and considers either the seller or the buyers choosing how much information to collect. We identify two channels through which having heterogeneous buyers make the decision increases social welfare: the full internalization of privacy costs and the customized choice of information levels. Perhaps surprisingly, the buyers voluntarily provide more information than what is mandatorily collected particularly when privacy is a significant concern, which often benefits the seller. Consumer and total welfare are increased with buyers choosing how much information to collect unless the external value of information is sufficiently large relative to the buyers’ privacy cost and heterogeneity in valuation. Given the growing privacy concerns surrounding personal data, our analysis supports offering consumers the autonomy, which can result in a Pareto improvement.
A self-consistent model for dust settling and the vertical shear instability in protoplanetary disks
Authors: Fukuhara Yuya , Okuzumi Satoshi
Published: May 2024

The spatial distribution of dust particles in protoplanetary disks affects dust evolution and planetesimal formation processes. The vertical shear instability (VSI) is one of the candidate hydrodynamic mechanisms that can generate turbulence in the outer disk region and affect dust diffusion. Turbulence driven by the VSI has a predominant vertical motion that can prevent dust settling. On the other hand, the dust distribution controls the spatial distribution of the gas cooling rate, thereby affecting the strength of VSI-driven turbulence. Here, we present a semi-analytic model that determines the vertical dust distribution and the strength of VSI-driven turbulence in a self-consistent manner. The model uses an empirical formula for the vertical diffusion coefficient in VSI-driven turbulence obtained from our recent hydrodynamical simulations. The formula returns the vertical diffusion coefficient as a function of the vertical profile of the cooling rate, which is determined by the vertical dust distribution. We use this model to search for an equilibrium vertical dust profile where settling balances with turbulent diffusion for a given maximum grain size. We find that if the grains are sufficiently small, there exists a stable equilibrium dust distribution where VSI-driven turbulence is sustained at a level of αz ∼ 10−3, where αz is the dimensionless vertical diffusion coefficient. However, as the maximum grain size increases, the equilibrium solution vanishes because the VSI can no longer stop the settling of the grains. This runaway settling may explain highly settled dust rings found in the outer part of some protoplanetary disks.
NudCL2 is required for cytokinesis by stabilizing RCC2 with Hsp90 at the midbody
Authors: Xu Xiaoyang , Huang Yuliang , Yang Feng , Sun Xiaoxia , Lin Rijin , Feng Jiaxing , Yang Mingyang , Shao Jiaqi , Liu Xiaoqi , Zhou Tianhua , Xie Shanshan , Yang Yuehong
Published: May 2024

Cytokinesis is required for faithful division of cytoplasmic components and duplicated nuclei into two daughter cells. Midbody, a protein-dense organelle that forms at the intercellular bridge, is indispensable for successful cytokinesis. However, the regulatory mechanism of cytokinesis at the midbody still remains elusive. Here, we unveil a critical role for NudC-like protein 2 (NudCL2), a co-chaperone of heat shock protein 90 (Hsp90), in cytokinesis regulation by stabilizing regulator of chromosome condensation 2 (RCC2) at the midbody in mammalian cells. NudCL2 localizes at the midbody, and its downregulation results in cytokinesis failure, multinucleation, and midbody disorganization. Using iTRAQ-based quantitative proteomic analysis, we find that RCC2 levels are decreased in NudCL2 knockout (KO) cells. Moreover, Hsp90 forms a complex with NudCL2 to stabilize RCC2, which is essential for cytokinesis. RCC2 depletion mirrors phenotypes observed in NudCL2-downregulated cells. Importantly, ectopic expression of RCC2 rescues the cytokinesis defects induced by NudCL2 deletion, but not vice versa. Together, our data reveal the significance of the NudCL2/Hsp90/RCC2 pathway in cytokinesis at the midbody.
Identifying giant cell arteritis patients with higher risk of relapse and vascular events: a cluster analysis
Authors: Guédon A F , Froger C , Agard C , Bénichou A , Le Jeune S , Mekinian A , Morard M , Skaff Y , De Boysson H , Espitia O
Published: May 2024

Objective

Giant cell arteritis (GCA) is one of the most common large vessel (LVV) vasculitis and is associated with a high risk of relapse and cardiovascular complications. Improving risk stratification remains a significant issue in this patient population. We aimed to perform a cluster analysis among GCA to identify clusters and evaluate their prognostic value.

Methods

In a multicenter cohort study, we performed hierarchical cluster analysis on the factor analysis of mixed data coordinates results with 283 GCA patients’ characteristics to generate clusters and assess incidence of relapse, cardiovascular events and death.

Results

Three clusters were identified: ‘Vascular relapsing profile’ (23.0%), ‘Typical GCA profile’ (47.7%) and ‘Ophthalmologic elderly profile’ (29.3%). The ‘Vascular relapsing profile’ cluster included younger patients with more frequent relapses and cardiovascular events, particularly thoracic aortic aneurysms. The ‘Typical GCA profile’ was the largest, with classic cranial manifestations and frequently associated polymyalgia rheumatica. The ‘Ophthalmologic elderly profile’ had the oldest patients with more visual loss and the highest mortality rate.

Conclusions

Our findings underline the varied prognostic landscape within GCA, emphasizing the poor cardiovascular prognosis of younger patients with LV involvement and the higher mortality among elderly patients. This reinforces the need for further research regarding the screening of aortic abnormalities and whether those patients might benefit from intensive treatment with biotherapy and cardiovascular risk factors management.
The practicalities of a partial lottery to allocate research funding
Authors: van der Meer Martijn , Antheunis Marjolijn L , Haverkort Boudewijn R
Published: May 2024

This article explores the practical dimension of organizing a partial lottery as an alternative funding allocation mechanism in academic institutions. Following an assessment of the recent literature that presents criticism of traditional ranking-based system derived from academic peer assessment and the need for improved decision-making procedures in research funding, we highlight four key arguments for organizing a partial lottery: improved decision quality (more fair, transparent, and divers), an alternative to ranking-based selection, prevention of questionable research practices, and increased efficiency. Based on our observations from a lottery-based ‘seed money call’ at Tilburg University, we provide insights into the organization and implementation of a lottery procedure, including the criteria for proposal eligibility, the administrative process, and the weighting mechanism based on budget categories. We furthermore share six lessons we learned that might be useful for future implementation in other institutional contexts, emphasizing the need for transparency, external supervision, and pre-registration of the lottery procedure to ensure trust and minimize gaming. As such, we not only contribute to the ongoing conceptual discussion about improving funding allocation mechanisms in academia. Our article also offers an account of how partial lotteries could be put into practice.