bluuebunny/crossref_metadata_2025 huggingface dataset:
Charged Pion Condensation and Color Superconductivity Phenomena in Chirally Asymmetric Dense Quark Matter
Authors: Khunjua T G , Klimenko K G , Zhokhov R N
Published: January 2025

In this paper, the question of the influence of color superconductivity on the formation of a phase with condensation of charged pions in dense, chirally asymmetric quark matter is studied. We consider it within the framework of the massless Nambu–Jona-Lasinio (NJL) model with a diquark interaction channel at zero temperature, but in the presence of baryon $\mu _B$, isospin $\mu _I$, chiral $\mu _{5}$, and chiral isospin $\mu _{I5}$ chemical potentials. It has been shown in the mean-field approximation that in the presence of chiral imbalance, when $\mu _{5}\ne 0$ and/or $\mu _{I5}\ne 0$, the color superconductivity phenomenon does not hinder the generation of charged pion condensation in dense quark matter even at the largest baryon densities attainable in heavy-ion collision experiments and in cores of neutron stars and their mergers, highlighting the resilience of this phase in dense quark matter. This makes the phase structure of dense quark matter even more rich, multifaceted, and interesting, and shows that pion condensation in dense quark matter is a viable phenomenon to be explored, e.g. in intermediate-energy heavy-ion collision experiments.
Impact of Finite Volume on Kaon, Antikaon, and ϕ Meson Masses and Decay Widths in Asymmetric Strange Hadronic Matter
Authors: Ahmad Zeeshan , Chahal Nisha , Kumar Arvind , Dutt Suneel
Published: January 2025

In the present work, we investigate the impact of finite volume on the in-medium properties of kaons ($K^+$, $K^0$), antikaons ($K^-$, $\bar{K^0}$), and $\phi$ mesons in the isospin asymmetric strange hadronic medium at finite density and temperature. We use the chiral SU(3) hadronic mean-field model, which accounts for the interactions between baryons through the exchange of scalar ($\sigma , \zeta , \delta$) and vector ($\omega$, $\rho$, $\phi$) fields. To investigate the effects of finite volume, we apply the multiple reflection expansion technique for calculations of the density of states. At high baryon density, an increase of the isospsin asymmetry of the medium from zero to a finite value is found to impact the nonstrange scalar field $\sigma$ more than the strange scalar field $\zeta$, whereas the opposite is the case as a function of the strangeness fraction of the medium. For example, in an infinite nuclear medium at $\rho _B = 4\rho _0$, for an increase of isospin asymmetry from zero to ${\sim}0.3$, the magnitudes of the scalar fields $\sigma$ and $\zeta$ increase by ${\sim}3.0$% and ${\sim}0.1$%, respectively. On the other hand, for a symmetric medium, an increase of $f_s$ from 0 to 0.5 leads to an increase in the magnitude of $\sigma$ by ${\sim}0.4$% and a decrease in $\zeta$ by ${\sim}16$%. We use the medium-modified masses of kaons and antikaons calculated using the chiral SU(3) model to obtain the masses and decay widths of $\phi$ mesons in the finite volume hadronic medium. To obtain the masses and decay widths of $\phi$ mesons, an effective Lagrangian approach with $\phi$K$\bar{K}$ interactions at the one-loop level is used in the present work. We obtain the effective masses and decay widths in the finite volume matter for a spherical geometry of a medium with Neumann and Dirichlet boundary conditions as well as for a cubic geometry. At baryon density 4$\rho _0$, the Dirichlet boundary conditions with spherical geometry of the medium leads to changes of ${\sim}4$%, ${\sim}3$%, and ${\sim}0.6$% in the effective masses of the K, $\bar{K}$, and $\phi$ mesons, as the system size decreases from $R = \infty$ to 2 fm in a symmetric nuclear medium.
Pseudorandomness of primes at large scales
Authors: Leung Sun-kai
Published: January 2025

Assuming a q-variant of the prime k-tuple conjecture uniformly, we compute mixed moments of the number of primes in disjoint short intervals and progressions. This involves estimating the mean of singular series along products of lattices, which is of independent interest. As a consequence, we establish the convergence of both sequences of suitably normalized primes to a standard Poisson point process.
Complement proteins in axial spondyloarthritis: associations with disease activity and TNFi treatment response in a multicentre RCT
Authors: Mistegaard Clara , Troldborg Anne , Torgutalp Murat , Loft Anne Gitte , Thiel Steffen , Muche Burkhard , Rios Rodriguez Valeria , Protopopov Mikhail , Listing Joachim , Sieper Joachim , Poddubnyy Denis , Proft Fabian
Published: January 2025

Objectives

To investigate lectin pathway proteins (LPPs) and complement activation marker C3dg as biomarkers for disease activity and treatment response in a multicentre, randomized controlled trial of axial spondyloarthritis (axSpA) patients initiating TNF inhibitor (TNFi) therapy.

Methods

Serum samples from 108 patients with active radiographic axSpA from the CONSUL study, collected before and after 12 weeks of TNFi therapy, were measured using immunoassays for LPPs (MBL, CL-L1, M-, L-, and H-ficolin, MASP-1, -2, and -3, MAp44) and the complement activation marker C3dg.

Results

After 12 weeks of TNFi therapy, serum levels of LPPs L-ficolin, M-ficolin, and MASP-2 decreased, while MASP-3 increased after adjustment for baseline CRP. Baseline L-ficolin levels correlated positively with baseline ASDAS-CRP and BASFI. C3dg correlated positively with ASDAS-CRP. Conversely, MASP-1 and MAp44 correlated negatively with ASDAS-CRP. Assessed by univariate logistic regression, C3dg and MASP-1 were associated with treatment response of clinically important improvement (ΔASDAS-CRP ≥1.1) and inactive disease (ASDAS-CRP <1.3) at week 12, respectively. Only C3dg remained significant in a multivariate regression analysis.

Conclusion

In this study, complement LPPs L-ficolin, M-ficolin, and MASP-2 levels decrease following initiation of TNFi therapy, whereas alternative pathway critical component MASP-3 increases. Baseline L-ficolin and C3dg correlated positively with ASDAS-CRP, potentially by CRP influence. Nevertheless, baseline C3dg levels were associated with treatment response (ASDAS-CRP <1.3) at week 12. Our results provide important perspectives on the inflammatory processes in axSpA, shedding light on the involvement of the complement system related to disease activity, treatment response, and potentially to prognosis.
matvis: a matrix-based visibility simulator for fast forward modelling of many-element 21 cm arrays
Authors: Kittiwisit Piyanat , Murray Steven G , Garsden Hugh , Bull Philip , Wilensky Michael J , Cain Christopher , Parsons Aaron R , Sipple Jackson , Adams Tyrone , Aguirre James E , Baartman Rushelle , Beardsley Adam P , Berkhout Lindsay M , Bernardi Gianni , Billings Tashalee S , Bowman Judd D , Bradley Richard F , Burba Jacob , Carey Steven , Carilli Chris L , Chen Kai-Feng , Choudhuri Samir , Cox Tyler , DeBoer David R , Acedo Eloy de Lera , Dexter Matt , Dillon Joshua S , Eksteen Nico , Ely John , Ewall-Wice Aaron , Fagnoni Nicolas , Furlanetto Steven R , Gale-Sides Kingsley , Gehlot Bharat Kumar , Glendenning Brian , Gorce Adelie , Gorthi Deepthi , Greig Bradley , Grobbelaar Jasper , Halday Ziyaad , Hazelton Bryna J , Hewitt Jacqueline N , Hickish Jack , Jacobs Daniel C , Josaitis Alec , Kern Nicholas S , Kerrigan Joshua , Kim Honggeun , Kolopanis Matthew , Lanman Adam , Plante Paul La , Liu Adrian , Ma Yin-Zhe , MacMahon David H E , Malan Lourence , Malgas Cresshim , Malgas Keith , Marero Bradley , Martinot Zachary E , McBride Lisa , Mesinger Andrei , Molewa Mathakane , Morales Miguel F , Mosiane Tshegofalang , Nunhokee Chuneeta Devi , Nuwegeld Hans , Pascua Robert , Qin Yuxiang , Rath Eleanor , Razavi-Ghods Nima , Robnett James , Santos Mario G , Sims Peter , Singh Saurabh , Storer Dara , Swarts Hilton , Tan Jianrong , Thyagarajan Nithyanandan , van Wyngaarden Pieter , Xu Zhilei , Zheng Haoxuan
Published: January 2025

Detection of the faint 21 cm line emission from the Cosmic Dawn and Epoch of Reionization will require not only exquisite control over instrumental calibration and systematics to achieve the necessary dynamic range of observations but also validation of analysis techniques to demonstrate their statistical properties and signal loss characteristics. A key ingredient in achieving this is the ability to perform high-fidelity simulations of the kinds of data that are produced by the large, many-element, radio interferometric arrays that have been purpose-built for these studies. The large scale of these arrays presents a computational challenge, as one must simulate a detailed sky and instrumental model across many hundreds of frequency channels, thousands of time samples, and tens of thousands of baselines for arrays with hundreds of antennas. In this paper, we present a fast matrix-based method for simulating radio interferometric measurements (visibilities) at the necessary scale. We achieve this through judicious use of primary beam interpolation, fast approximations for coordinate transforms, and a vectorized outer product to expand per-antenna quantities to per-baseline visibilities, coupled with standard parallelization techniques. We validate the results of this method, implemented in the publicly available matvis code, against a high-precision reference simulator, and explore its computational scaling on a variety of problems.
Extinct scorpion family Chaerilobuthidae from Mid-Cretaceous Burmese amber reinterpreted as subfamily of extant family Pseudochactidae (Chelicerata: Scorpiones)
Authors: Xuan Qiang , Prendini Lorenzo , Engel Michael S , Cai Chenyang , Huang Diying
Published: January 2025

The extinct scorpion family Chaerilobuthidae Lourenço and Beigel, 2011, endemic to Burmese amber, was initially established due to its unique pedipalp trichobothrial pattern related to the Type A and Type B patterns of families Buthidae C.L. Koch, 1837 and Chaerilidae Pocock, 1893, respectively. The present contribution describes 11 new specimens, representing seven species of Chaerilobuthidae from Mid-Cretaceous Burmese amber, revealing their morphology using various imaging technologies. A revised diagnosis of Chaerilobuthus Lourenço and Beigel, 2011 is provided based on new morphological characters of the carapace, ocelli, chelicera, pedipalp trichobothria, coxapophyses, and leg tarsi. The other two genera of Chaerilobuthidae, Chaeriloiurus Lourenço, 2020 and Serratochaerilobuthus Lourenço, 2024, are synonymized with Chaerilobuthus based on a reassessment of their morphological characters and morphometric analysis, creating Chaerilobuthus brigittemuellerae (Lourenço and Velten, 2020), comb. nov. and Chaerilobuthus schmidti (Lourenço and Velten, 2024), comb. nov.. The systematic position of Chaerilobuthidae is clarified based on phylogenetic analyses of an updated morphological character matrix for Pseudochactidae Gromov, 1998, an extant family in Asia. Phylogenetic analysis placed Chaerilobuthidae sister to the pseudochactid subfamily Vietbocapinae Lourenço, 2012, justifying its transfer to Pseudochactidae, as Chaerilobuthinae Lourenço and Beigel, 2011, stat. nov.. This discovery confirms that Pseudochactidae date back 100 Mya and contributes to understanding the origin and evolutionary history of this relictual family.
Degree of Preoperative Bilateral Hearing Affects Patient-Reported Outcome in Primary Stapedotomy
Authors: Thunberg Ulrica , Tahir Taj , Redfors Ylva Dahlin , Finizia Caterina
Published: January 2025

Objective

To investigate whether degree of asymmetric hearing impairment influences patient-reported outcome measures and objective hearing results in primary stapedotomy.

Study Design

Register study.

Setting

Data from the Swedish Quality Register for Otosclerosis Surgery consisting of 90% of stapes operations performed in Sweden

Main Outcome measure

The 984 patients eligible for inclusion were categorized on the basis of preoperative hearing impairment: unilateral, bilateral asymmetric, or bilateral symmetric. Pure-tone audiometry and patient-reported outcome measures were analyzed, and Glasgow benefit plots were constructed. Ordinal logistics regression analyses were performed to adjust for factors influencing PROMs associated with degree of asymmetric hearing.

Results

Over 90% of patients across all groups reported improved or much improved hearing ability post-surgery. Ninety-five percent of patients who rated their hearing as worse or much worse after surgery had an air-conductive gain of <20 dB PTA4. Individuals with unilateral hearing impairment were more likely to report lower satisfaction with hearing function and daily life activities after surgery compared with those with bilateral hearing impairment, especially bilateral symmetric hearing impairment. In terms of hearing function, the bilateral symmetric hearing impairment group showed a significant decrease in the log odds of reporting lower satisfaction with a coefficient of −0.71 (95% confidence interval, −1.13 to −0.33), whereas the bilateral asymmetric hearing impairment group showed a nonsignificant decrease with a coefficient of −0.14 (95% confidence interval, −0.41 to 0.14) compared with the unilateral hearing impairment group. Tinnitus was more frequent in those with unilateral hearing impairment.

Conclusion

Those with preoperative unilateral hearing impairment were more likely to express lower satisfaction with the results, compared with patients with bilateral impairment. Our findings suggest that the degree of bilateral hearing impairment should be considered in preoperative counseling, to better align with patient expectations regarding the benefit of surgery. An estimated air-conductive gain of at least 20 dB PTA4 was favorable for patient satisfaction.
Effect of Patient Positioning on CT Number Accuracy: A Phantom Study Comparing Energy Integrating and Deep Silicon Photon Counting Detector CT
Authors: Salyapongse Aria M. , Rose Sean D. , Pickhardt Perry J. , Lubner Meghan G. , Toia Giuseppe V. , Bujila Robert , Yin Zhye , Slavic Scott , Szczykutowicz Timothy P.
Published: January 2025

Objective

Patient positioning during clinical practice can be challenging, and mispositioning leads to a change in CT number. CT number fluctuation was assessed in single-energy (SE) EID, dual-energy (DE) EID, and deep silicon photon-counting detector (PCD) CT over water-equivalent diameter (WED) with different mispositions.

Methods

A phantom containing five clinically relevant inserts (Mercury Phantom, Gammex) was scanned on a clinical EID CT and a deep silicon PCD CT prototype at vertical positions of 0, 4, 8, and 12 cm. EID scans used 120 kV and rapid kV-switching DE techniques. CT number was calculated for air, water, polystyrene, iodine 10 mg/mL, and bone. Ideal CT numbers were calculated using the NIST XCOM database toolkit. Comparison of measured to ideal CT number utilized relative root mean square error (RMSE). Trends in CT number versus WED were compared using linear regression and statistical comparisons to test for differences in slope.

Results

No statistical difference of CT number with mispositioning was seen between acquisition modes. CT number fluctuation was larger due to WED than mispositioning for all material inserts. Water, iodine, and bone, for deep silicon PCD CT had statistically significant (P < 0.05) smaller slopes compared to EIDof CT number over WED for all tested mispositions. The accuracy of deep silicon PCD CT was higher than either SE or DE EID CT for all materials at all mispositions except for polystyrene.

Conclusions

WED (ie, patient size) contributes to CT number fluctuation more than mispositioning. The change in CT number was significantly smaller, and CT number accuracy was higher for deep silicon PCD CT in this phantom study.
Pilot Study Examining the Use of DCE MRI With Pharmacokinetic Analysis to Evaluate Hypoxia in Prostate Cancer
Authors: Febronio Eduardo Miguel , Secaf André de Freitas , Chahud Fernando , Elias Jorge , Reis Rodolfo B. , Muglia Valdair F.
Published: January 2025

Purpose:

This study aimed to investigate the association between tumor hypoxia, assessed through anti-HIF (hypoxia-inducible factor) staining, and aggressiveness in prostate cancer using a pharmacokinetic model, particularly those derived from the Tofts model, in predicting tumor aggressiveness.

Material and Methods:

From January 2019 to April 2021, we conducted a retrospective search of patients with confirmed prostate cancer and a previous magnetic resonance imaging (MRI) examination. After exclusions, a total of 57 consecutive patients were enrolled. Patient data, including demographic, laboratory, and pathologic variables, were collected. MRI acquisition followed PI-RADS guidelines, encompassing T2-weighted, diffusion-weighted imaging, and dynamic contrast-enhanced imaging. An experienced abdominal radiologist conducted both morphologic and quantitative MRI analyses, evaluating parameters such as lesion size, apparent diffusion coefficient values, and the Tofts pharmacokinetics (TF) model. The histopathologic analysis included the International Society of Uropathology (ISUP) score and hypoxia marker immunohistochemistry.

Results:

There were no significant demographic and imaging differences between hypoxic and nonhypoxic tumors, except for elevated prostate-specific antigen levels in the latter and decreased normalized apparent diffusion coefficient in the former. Morphologic assessments revealed larger lesions in the hypoxia group. While K
trans showed a positive association with hypoxia, it did not independently predict high-risk lesions.

Conclusions:

Our results suggest that pharmacokinetic analysis by the Tofts model was associated with tumors with hypoxia. However, this parameter was not an independent predictor of more aggressive tumors. Further studies, with a larger number of patients, multi-institutional and prospective, are needed to verify this possible association.
Dual-Split CT to Simulate Multiple Radiation Doses From a Single Scan—Liver Lesion Detection Compared With Dose-Matched Single-Energy CT
Authors: Racine Damien , Niemann Tilo , Nemeth Bence , Manzano Lucia Gallego , Alkadhi Hatem , Viry Anaïs , Kubik-Huch Rahel A. , Frauenfelder Thomas , Euler André
Published: January 2025

Objectives

The aim of this study was to evaluate the potential use of simulated radiation doses from a dual-split CT scan for dose optimization by comparing their lesion detectability to dose-matched single-energy CT acquisitions at different radiation dose levels using a mathematical model observer.

Materials and Methods

An anthropomorphic abdominal phantom with liver lesions (5–10 mm, both hyperattenuating and hypoattenuating) was imaged using a third-generation dual-source CT in single-energy dual-source mode at 100 kVp and 3 radiation doses (5, 2.5, 1.25 mGy). The tube current was 67% for tube A and 33% for tube B. For each dose, 5 simulated radiation doses (100%, 67%, 55%, 45%, 39%, and 33%) were generated through linear image blending. The phantom was also imaged using traditional single-source single-energy mode at equivalent doses. Each setup was repeated 10 times. Image noise texture was evaluated by the average spatial frequency (fav) of the noise power spectrum. Liver lesion detection was measured by the area under the receiver operating curve (AUC), using a channelized Hotelling model observer with 10 dense Gaussian channels.

Results

Fav decreased at lower radiation doses and differed between simulated and single-energy images (eg, 0.16 mm−1 vs 0.14 mm−1 for simulated and single-energy images at 1.25 mGy), indicating slightly blotchier noise texture for dual-split CT. For hyperattenuating lesions, the mean AUC ranged between 0.92–0.99, 0.81–0.96, and 0.68–0.89 for single-energy, and between 0.91–0.99, 0.78–0.91, and 0.70–0.85 for dual-split at 5 mGy, 2.5 mGy, and 1.25 mGy, respectively. For hypoattenuating lesions, the AUC ranged between 0.90–0.98, 0.75–0.93, and 0.69–0.86 for the single-energy, and between 0.92–0.99, 0.76–0.87, and 0.67–0.81 for dual-split at 5 mGy, 2.5 mGy, and 1.25 mGy, respectively. AUC values were similar between both modes at 5 mGy, and slightly lower, albeit not significantly, for the dual-split mode at 2.5 and 1.25 mGy.

Conclusions

Lesion detectability was comparable between multiple simulated radiation doses from a dual-split CT scan and dose-matched single-energy CT. Noise texture was slightly blotchier in the simulated images. Simulated doses using dual-split CT can be used to assess the impact of radiation dose reduction on lesion detectability without the need for repeated patient scans.
Anin vitroplatform for characterizing axonal electrophysiology of individual human iPSC-derived nociceptors
Authors: Clément Blandine F. , Petrella Lorenzo , Wallimann Lea , Duru Jens , Tringides Christina M. , Vörös János , Ruff Tobias
Published: January 2025

Current treatments against severe forms of neuropathic pain demonstrate insufficient efficacy or lead to unwanted side effects as they fail to specifically target the affected nociceptors - a specialized subclass of sensory neurons conveying potentially damaging stimuli information to the central nervous system. Neuropathic pain may involve different nociceptor subtypes in different patients. Tools that can distinguish nociceptive axons would enable a more targeted compound screening. Therefore, we developed anin vitroplatform combining a CMOS-based high-density microelectrode array with a polydimethylsiloxane (PDMS) guiding microstructure that captures the electrophysiological responses of nociceptors. Human induced pluripotent stem cell-derived (iPSC) nociceptors were cultured at low density with axons distributed through parallel 4 × 10 µm microchannels exiting the seeding well before converging to a bigger axon-collecting channel. This configuration allowed the measurement of stimulation-induced responses of individual axons. Nociceptors were found to exhibit a great diversity of electrophysiological response profiles that can be classified into different functional archetypes. Moreover, we show that some responses are affected by applying the TRPV1 agonist capsaicin. Overall, results using our platform demonstrate that we were able to distinguish nociceptive axons from different subtypes. The platform provides a promising tool for screening potential candidates for nociceptor-specific drugs.
Lithography-free Water Stable Conductive Polymer Nanowires
Authors: Hughes Damien , Mousa Abdelrazek H. , Musumeci Chiara , Larsson Malte , Shameem Muhammad Anwar , Aydemir Umut , Schmiderer Ludwig , Larsson Jonas , Berggren Magnus , Ek Fredrik , Olsson Roger , Hjort Martin
Published: January 2025

Free-standing nanowires can gain intracellular access without causing cellular stress or apoptosis. Current approaches to generate nanowires focus on lithographic patterning and inorganic materials (Si, GaAs, Al2O3, etc.) while organic materials are less explored. Use of organic conductive polymers allows for creation of soft mixed ion–electron conducting nanowires. Processing conductive polymers into nanowires is challenging due to the harsh chemicals and processing conditions used. Here, we demonstrate a lithography-free and scalable method to generate all-organic water-stable nanowires composed of conductive polymers. A nanoporous membrane is filled with conductive polymer in solution followed by a cross-linking step to make the polymer water stable. The surface of the membrane is anisotropically etched using a reactive ion etcher to reveal the polymer inside the pores, which extend from the membrane as nanowires. We interface the nanowires with model algal cells and human primary hematopoietic stem and progenitor cells.

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Minimally Invasive DNA-Mediated Photostabilization for Extended Single-Molecule and Super-resolution Imaging
Authors: Scheckenbach Michael , Close Cindy , Bauer Julian , Grabenhorst Lennart , Cole Fiona , Köhler Jens , Matikonda Siddharth S. , Zhang Lei , Cordes Thorben , Schnermann Martin J. , Herrmann Andreas , Tinnefeld Philip , Szalai Alan M. , Glembockyte Viktorija
Published: January 2025

Photobleaching of fluorescence labels poses a major limitation in single-molecule and super-resolution microscopy. Conventional photostabilization methods, such as oxygen removal and addition of high concentrations of photostabilization additives, often require careful fluorophore selection and can disrupt the biological environment. To address these limitations, we developed a modular and minimally invasive photostabilization approach that utilizes DNA-mediated delivery of a photostabilizer directly to the imaging site. Under lower excitation intensities, the DNA-mediated strategy outperformed solution-based approaches, achieving efficient photostabilization at significantly lower additive concentrations. However, at higher excitation intensities, the stability of a single photostabilizer molecule became the limiting factor. To overcome this and reduce the loss of localizations in DNA-PAINT experiments we have also implemented a recovery scheme where the photostabilizer is continuously replenished at the imaging site. We further extended the approach to cell imaging, demonstrating improved localization rate and precision in 3D-DNA PAINT measurements. DNA-mediated photostabilization offers a promising solution for imaging applications where high additive concentrations are prohibited. Its modularity enables adaptation to various imaging schemes and ultimately expands the repertoire of fluorophores suitable for single-molecule and super-resolution imaging.
Revisiting the Central Dogma: the distinct roles of genome, methylation, transcription, and translation on protein expression inArabidopsis thaliana
Authors: Zhong Ziming , Bailey Mark , Kim Yong-In , Afsharyan Nazanin P. , Parker Briony , Arathoon Louise , Li Xiaowei , Rundle Chelsea A. , Behrens Andrew , Nedialkova Danny , Slavov Gancho , Hassani-Pak Keywan , Lilley Kathryn S. , Theodoulou Frederica L. , Mott Richard
Published: January 2025

Background

We investigated the flow of information from genome sequence to protein expression implied by the Central Dogma, to determine the impact of intermediate genomic levels in plants.

Results

We performed genomic profiling of rosettes in twoArabidopsisaccessions, Col-0 and Can-0, and assembled their genomes using long reads and chromatin interaction data. We measured gene and protein expression in biological replicates grown in a controlled environment, also measuring CpG methylation, ribosome-associated transcript levels and tRNA abundance. Each omic level is highly reproducible between biological replicates and between accessions despite their 0.5% sequence divergence; the single best predictor of any level in one accession is the corresponding level in the other. Within each accession, gene codon frequencies accurately model both mRNA and protein expression. The effects of a codon on mRNA and protein expression are highly correlated but are unrelated to genome-wide codon frequencies or to tRNA levels which instead match genome-wide amino acid frequencies. Ribosome-associated transcripts closely track mRNA levels.

Conclusions

In the absence of environmental perturbation, neither methylation, tRNA nor ribosome-associated transcript levels add appreciable information about constitutive protein abundance beyond that in DNA codon frequencies and mRNA expression levels. The impact of constitutive gbM is mostly explained by gene codon composition. tRNA abundance tracks overall amino acid demand. However, genetic differences between accessions associate with differential gbM by inflating differential expression variation. Our data show that the Central Dogma holds only if both sequence and abundance information in mRNA are considered.
Antarctic photosynthesis: energy transfer and charge separation in the diatomChaetoceros Simplex
Authors: Lee Shu En , van de Poll Willem , Chukhutsina Volha
Published: January 2025

The polar oceanic environment poses extreme challenges to photosynthetic organisms, which have evolved atypical strategies to maintain efficient photosynthesis in cold temperatures. Here, the psychrophilic diatomChaetoceros simplex (C. simplex)is studiedin vivoin the dark-adapted state using steady-state and time-resolved fluorescence methods. Our results show that all fucoxanthin chlorophyll a/c protein (FCP) antenna transfer energy to photosystem I (PSI) or photosystem II (PSII), with no detached FCPs. PSI exhibits no fluorescence of ‘red’ forms of chlorophyll (chl) beyond 700 nm in both 279 K and 77 K conditions. Despite this, it apparently has a long decay time of ∼85 ps indicating the presence of a large core-antenna supercomplex. PSII has an average lifetime of ∼500ps in open state (QAoxidized) and ∼1220 ps in closed state (QAreduced). PSII of C. simplex has kinetics that are slightly slower than temperate diatoms, suggesting slightly larger antenna. In addition, fucoxanthin (fx) molecules of FCP that absorb in the 500 - 550 nm range (fx-red) transfer more energy to PSII than fx that absorb in the blue range (fx-blue, 462 nm max absorption). A subpopulation of red-shifted, aggregated FCPs are detected at 77 K, that are active in energy transfer uphill at 279 K. Overall, our results indicate relatively larger antenna of PSI and PSII and an absence of red chls in PSI of cold-adapted species, compared to temperate species.
Atomistic Mechanism of Non-Canonical Voltage Gating in TREK K2PChannels
Authors: Aldakul Yessenbek K. , Schewe Marcus , Diez Carlos C. , Hwang Songhwan , Baukrowitz Thomas , Sun Han
Published: January 2025

Two-pore-domain K+(K2P) channels are essential regulators of cellular excitability and respond to various external stimuli that also include membrane potential for most K2Pchannels. Voltage gating is particularly pronounced in members of the TREK/TRAAK subfamily. This voltage sensitivity was surprising, as K2Pchannels lack a classical voltage sensing domain. Prior studies have attributed this non-canonical voltage sensing mechanism to the unique ion-flux gating properties of the K2Pselectivity filter (SF), where inward currents induce fast inactivation, while depolarization activates the SF. Here, we performed large-scale molecular dynamics (MD) simulations across various voltages to gain an atomistic understanding of ion-flux gating in TREK channels. Our analysis revealed an asymmetric stability difference in the SF, enabling water influx into the filter due to conformational flexibility on the extracellular side. Inward flux inactivation occurs when water entry halts ion permeation, followed by the unbinding of three K+ions, consistent with gating charge analysis. Additionally, MD simulations of TREK-2 mutants and the TWIK-1 channel, which exhibited increased SF flexibility, showed augmented SF water occupancy, aligning with their electrophysiological phenotypes. Key experimental evidence of this mechanism was provided by electrophysiology measurements, which showed that high extracellular sucrose slowed ion-flux inactivation by reducing water entry into the SF. These findings uncover the atomistic mechanism of voltage gating in TREK K2Pchannels and pave the way for exploring non-canonical voltage gating mechanisms in other ion channels.
Engineering Infrared Light Detection in Blind Human Retina Using Ultrasensitive Human TRPV1 Channels
Authors: Chevalier Morgan , Fadel Firas , Májer Tímea , Magda Dániel Péter , Gerendás Lili , Kilin Ferenc , Nagy Zoltán Zsolt , Szabó Arnold , Roska Botond , Testa-Silva Guilherme
Published: January 2025

Engineering infrared light sensitivity in the blind human retina could restore visual function in patients with regional retinal degeneration. However, current approaches are complex and contain non-human biological components. Using rational protein design we engineered human TRPV1 channels (Δ786-840) with temperature sensitivity shifted from 45 to 41°C that enabled near-infrared light- induced heat activation of mammalian cells at close to physiological temperatures. When expressed in ganglion cells of human retinal explants, Δ786-840 TRPV1 generated robust spiking responses to brief near-infrared light-induced temperature transients. Additionally, increasing intensity of radiation evoked graded responses correlating with increasing firing frequencies. Unlike previous approaches that used non-human TRPV1 channels, which risk immune reactions and a multicomponent system that poses barriers to clinical implementation, this single component human-derived approach eliminates immunogenicity concerns, addressing a major challenge to clinical translation, and allow gene delivery using adeno-associated viral vectors.
VE-cadherin RGD motifs are dispensable for cell-cell junctions, endothelial barrier function and leukocyte extravasation
Authors: Schoon Rianne M. , van der Meer Werner J. , van Stalborch Anne-Marieke D. , van Buul Jaap D. , Huveneers Stephan
Published: January 2025

VE-cadherin is a key transmembrane protein in endothelial cell-cell junctions, essential for maintaining vascular integrity and regulating selective leukocyte extravasation into inflamed tissue. The extracellular domain of human VE-cadherin contains two arginine-glycine-aspartate (RGD) motifs, which are known integrin-binding sites, particularly for integrins in the β1, β3, and β5 families. In this study, we examined the functional relevance of these RGD motifs by generating VE-cadherin variants with the RGD sequences mutated to non-functional RGE. Immunofluorescence analysis showed that the VE-cadherin[D238E], VE-cadherin[D301E], and double-mutant VE-cadherin[D238/301E] variants formed stable cell-cell junctions, comparable to wild-type VE-cadherin. Additionally, electric cell-substrate impedance sensing (ECIS) confirmed that endothelial cells expressing each VE-cadherin RGD>RGE variant maintained efficient barrier function. Moreover, leukocyte transmigration assays demonstrated that the RGD>RGE mutations did not affect leukocyte-endothelial interactions during transmigration. In summary, our findings indicate that the VE-cadherin RGD motifs are not essential for endothelial junction formation or leukocyte transmigration.
Sex chromosomes and chromosomal rearrangements are key to behavioural sexual isolation in Jaera albifrons marine isopods
Authors: Ribardiere Ambre , Daguin-Thiebaut Claire , Coudret Jerome , Le Corguille Gildas , Avia Komlan , Houbin Celine , Loisel Stephane , Gagnaire Pierre-Alexandre , Broquet Thomas
Published: January 2025

The lack of sexual attraction between individuals from different populations is a direct barrier to gene flow between these populations. Here we focus on the evolution of this class of isolating mechanism, behavioural sexual isolation, through the empirical study of two closely related species of small marine isopods. The males of Jaera albifrons and J. praehirsuta similarly engage females in tactile courtship by brushing a specific region of the female's back, but they do so with divergent sets of specialised setae and spines, and female choice results in strong reproductive isolation. Using bi-allelic SNP genotypes obtained from double-digest RAD sequencing of individuals from natural populations and controlled crosses, we found that secondary contacts between J. albifrons and J. praehirsuta resulted in different levels of heterospecific gene flow depending on the ecological context. Comparison of the genomic landscapes of differentiation in the two most contrasting situations (extremely low heterospecific gene flow in one region of western France, but strong introgressive hybridisation in another), combined with linkage map analyses, allowed us to conclude that genomic regions impervious to interspecies gene flow are located either on the sex chromosomes or on rearranged chromosomes (several fusion-scissions and one reciprocal translocation). These genomic regions show low recombination, and in two cases QTL analyses found genetic variation associated with several male courtship traits. These results suggest that a long period of allopatry may have allowed the divergent co-evolution of male traits and female preferences, with genetic bases located at least in part in non-recombining regions on sex chromosomes and rearranged chromosomes.
Rapid “recycling” of logical algorithm representations in fronto-parietal reasoning systems following computer programming instructions
Authors: Liu Yun-Fei , Bedny Marina
Published: January 2025

Programming is a cornerstone of modern society, yet its cognitive and neural basis remains poorly understood. In this study, we test the hypothesis that programming “recycles” pre-existing neural mechanisms and representations in fronto-parietal reasoning networks. Using fMRI, we scanned programming-naïve undergraduates (n=22) before (PRE) and after (POST) an introductory Python course. During the PRE scan, participants viewed pseudocode (plain English descriptions of algorithms), and during the POST scan, they read Python code. We found that a left-lateralized fronto-parietal network, previously implicated in programming experts, distinguished between “for” loops and “if” conditionals across both pseudocode and Python code. Representational similarity analysis revealed consistent representations of algorithms across formats (code/pseudocode) and learning stages. Furthermore, such representations encode abstract meanings rather than superficial features. Our findings demonstrate that programming not only recycles pre-existing neural resources evolved for logical reasoning, but the recycling takes place rapidly with only a single semester of training.
Modeling human limb skeletal development using human pluripotent stem cell-derived skeletal assembloids
Authors: Takao Tomoka , Osone Tatsunori , Sato Kohei , Yamada Daisuke , Fujisawa Yuki , Hagiwara Masaya , Nakata Eiji , Ozaki Toshifumi , Toguchida Junya , Takarada Takeshi
Published: January 2025

Despite recent advances in pluripotent stem cell-based approaches to induce skeletal cells, recapitulating human limb skeletal development in terms of structure and longitudinally oriented growth remains an unresolved challenge. Here, we report a method to differentiate human pluripotent stem cells into region-specific skeletal organoids harboring GDF5+PRG4+interzone/articular chondrocyte progenitors (IZ/ACPs) and SP7+growth plate chondrocytes (GPCs) via PRRX1+limb-bud mesenchymal cells. Comparative analysis demonstrated marked similarities of IZ/ACP and GPC organoids to the human embryonic limb, and graft fate and regenerative capacityin vivowere further characterized. We also mimicked the limb skeletal developmental process in a spatially structured manner by vertically positioning two IZ/ACP organoids at both ends of a GPC organoid to generate a human skeletal assembloid. Notably, this human skeletal assembloid recapitulated endochondral ossification with longitudinal skeletal growth upon transplantation. In summary, our study provides a novel research platform for human limb skeletal development and disease.
Inherent instability of simple DNA repeats shapes an evolutionarily stable distribution of repeat lengths
Authors: McGinty Ryan J. , Balick Daniel J. , Mirkin Sergei M. , Sunyaev Shamil R.
Published: January 2025

Using the Telomere-to-Telomere reference, we assembled the distribution of simple repeat lengths present in the human genome. Analyzing over two hundred mammalian genomes, we found remarkable consistency in the shape of the distribution across evolutionary epochs. All observed genomes harbor an excess of long repeats, which are prone to developing into repeat expansion disorders. We measured mutation rates for repeat length instability, quantitatively modeled the per-generation action of mutations, and observed the corresponding long-term behavior shaping the repeat length distribution. We found that short repetitive sequences appear to be a straightforward consequence of random substitution. Evolving largely independently, longer repeats (10+ nucleotides) emerge and persist in a rapidly mutating dynamic balance between expansion, contraction and interruption. These mutational processes, collectively, are sufficient to explain the abundance of long repeats, without invoking natural selection. Our analysis constrains properties of molecular mechanisms responsible for maintaining genome fidelity that underlie repeat instability.
Genome-wide CRISPR knockout screening with viral replicons for identification of host factors involved in viral replication
Authors: Cheng Karen W. , Bhave Madhura , Markhard Andrew , Peng Duo , Bhatt Karan D. , Travisano Katherine , Medicielo Josette V. , Lembirik Sanae , Njoya Leila , Anantpadma Manu , Kuhn Jens H. , Puschnik Andreas S. , Kistler Amy
Published: January 2025

Pooled CRISPR knockout (KO) screens using live viruses are a proven and valuable approach for identifying essential host factors acting across viral life cycles. Here we describe the development of a pooled genome-wide CRISPR KO screening approach using stable viral replicon cell lines to specifically identify host factors essential for viral replication. Virus replicons are non-infectious, therefore enabling the study of highly virulent viruses under standard biosafety level 2 containment. We developed a stable fluorescent dengue virus type 2 (DENV-2) replicon cell line to perform a pooled genome-wide FACS-based CRISPR KO screen. This benchmark DENV-2 replicon screen successfully identified host genes previously known to be required for viral DENV-2 replication (e.g., endoplasmic reticulum membrane complex and oligosaccharyltransferase complex components) and confirmed two additional genes (DOHH and ZFP36L2) involved in replication that have not been recovered in prior live virus screens. We applied this replicon screening approach to two highly divergent viruses: chikungunya virus (CHIKV), a positive-sense RNA virus that replicates at the plasma membrane, and Ebola virus (EBOV), a negative-sense RNA virus that replicates in cytoplasmic inclusion bodies. The CHIKV replicon screen identified two genes known to be required for replication (G3BP1 and G3BP2) and several additional, novel genes (CLEC4G, CSDE1, GOLGA7, HNF1A, and PCBD1). We verified two of them (CSDE1 and GOLGA7) in live CHIKV replication assays. A distinct set of genes (EHMT1, EHMT2, and USP7) were recovered in the EBOV replicon screen and were further confirmed using independent transient transfection assays. Thus, viral replicon-based screens provide a useful approach that can be extended to viruses of diverse taxa to identify host pathways essential for viral replication and to uncover potential novel targets for host-directed medical countermeasures.
Neural mechanisms of object prioritization in vision
Authors: Grignolio Damiano , Meyyappan Sreenivasan , Geng Joy , Mangun George R. , Hickey Clayton
Published: January 2025

Selective attention is widely thought to be sensitive to visual objects. This is commonly demonstrated in cueing studies, which show that when attention is deployed to a known target location that happens to fall on a visual object, responses to targets that unexpectedly appear at other locations on that object are faster and more accurate, as if the object in its entirety has been visually prioritized. However, this notion has recently been challenged by results suggesting that putative object-based effects may reflect the influence of hemifield anisotropies in attentional deployment, or of unacknowledged influences of perceptual complexity and visual clutter. Studies employing measures of behaviour provide limited opportunity to address these challenges. Here, we used EEG to directly measure the influence of task-irrelevant objects on the deployment of visual attention. We had participants complete a simple visual cueing task involving identification of a target that appeared at either a cued location or elsewhere. Throughout each experimental trial, displays contained task-irrelevant rectangle stimuli that could be oriented horizontally or vertically. We derived two cue-elicited indices of attentional deployment–lateralized alpha oscillations and the ADAN component of the event-related potential–and found that these were sensitive to the otherwise irrelevant orientation of the rectangles. Our results demonstrate that the allocation of visual attention is influenced by objects boundaries, supporting models of object-based attentional prioritization.
N6-methyladenosine and the NEXT complex direct Xist RNA turnover and X inactivation dynamics
Authors: Wei Guifeng , Coker Heather , Rodermund Lisa , Almeida Mafalda , Roach Holly L. , Nesterova Tatyana B. , Brockdorff Neil
Published: January 2025

X chromosome inactivation (XCI) in mammals is orchestrated by the non-coding RNA Xist which together with specific interacting proteins, functionsin cisto silence an entire X chromosome. Defined sites on Xist RNA carry theN6-methyladenosine (m6A) modification, and perturbation of the m6A writer complex has been found to abrogate Xist-mediated gene-silencing. However, the relative contribution of m6A and its mechanism of action remain unclear. Here we investigate the role of m6A in XCI by applying rapid degron-mediated depletion of METTL3, the catalytic subunit of the m6A writer complex, an approach that minimises indirect effects due to transcriptome-wide depletion of m6A. We find that acute loss of METTL3/m6A accelerates Xist-mediated gene silencing, and that this correlates with increased levels and stability of Xist transcripts. We show that Xist RNA turnover is mediated by the nuclear exosome targeting (NEXT) complex but is independent of the principal nuclear m6A reader protein YTHDC1. Our findings demonstrate that the primary function of m6A on Xist RNA is to promote Xist RNA turnover which in turn regulates XCI dynamics.
Design of SARS-CoV-2 RBD Immunogens to Focus Immune Responses Towards Conserved Coronavirus Epitopes
Authors: Harris Caitlin , Kapingidza A. Brenda , San James E. , Christopher Jayani , Gavitt Tyler , Rhodes Brianna , Janowska Katarzyna , O’Donnell Christopher , Lindenberger Jared , Huang Xiao , Sammour Salam , Berry Madison , Barr Maggie , Parks Rob , Newman Amanda , Overton Mary , Oguin Thomas , Acharya Priyamvada , Haynes Barton F. , Saunders Kevin O. , Wiehe Kevin , Azoitei Mihai L.
Published: January 2025

SARS-CoV-2 continues to evolve, with new variants emerging that evade pre-existing immunity and limit the efficacy of existing vaccines. One approach towards developing superior, variant-proof vaccines is to engineer immunogens that preferentially elicit antibodies with broad cross-reactivity against SARS-CoV-2 and its variants by targeting conserved epitopes on spike. The inner and outer faces of the Receptor Binding Domain (RBD) are two such conserved regions targeted by antibodies that recognize diverse human and animal coronaviruses. To promote the elicitation of such antibodies by vaccination, we engineered “resurfaced” RBD immunogens that contained mutations at exposed RBD residues outside the target epitopes. In the context of pre-existing immunity, these vaccine candidates aim to disfavor the elicitation of strain-specific antibodies against the immunodominant Receptor Binding Motif (RBM) while boosting the induction of inner and outer face antibodies. The engineered resurfaced RBD immunogens were stable, lacked binding to monoclonal antibodies with limited breadth, and maintained strong interactions with target broadly neutralizing antibodies. When used as vaccines, they limited humoral responses against the RBM as intended. Multimerization on nanoparticles further increased the immunogenicity of the resurfaced RBDs immunogens, thus supporting resurfacing as a promising immunogen design approach to rationally shift natural immune responses to develop more protective vaccines.