bluuebunny/crossref_metadata_2025 huggingface dataset:
PRPF8-mediated dysregulation of hBrr2 helicase disrupts human spliceosome kinetics and 5´-splice-site selection causing tissue-specific defects
Authors: Atkinson Robert , Georgiou Maria , Yang Chunbo , Szymanska Katarzyna , Lahat Albert , Vasconcelos Elton J. R. , Ji Yanlong , Moya Molina Marina , Collin Joseph , Queen Rachel , Dorgau Birthe , Watson Avril , Kurzawa-Akanbi Marzena , Laws Ross , Saxena Abhijit , Shyan Beh Chia , Siachisumo Chileleko , Goertler Franziska , Karwatka Magdalena , Davey Tracey , Inglehearn Chris F. , McKibbin Martin , Lührmann Reinhard , Steel David H. , Elliott David J. , Armstrong Lyle , Urlaub Henning , Ali Robin R. , Grellscheid Sushma-Nagaraja , Johnson Colin A. , Mozaffari-Jovin Sina , Lako Majlinda
Published: April 2024

The carboxy-terminus of the spliceosomal protein PRPF8, which regulates the RNA helicase Brr2, is a hotspot for mutations causing retinitis pigmentosa-type 13, with unclear role in human splicing and tissue-specificity mechanism. We used patient induced pluripotent stem cells-derived cells, carrying the heterozygous PRPF8 c.6926 A > C (p.H2309P) mutation to demonstrate retinal-specific endophenotypes comprising photoreceptor loss, apical-basal polarity and ciliary defects. Comprehensive molecular, transcriptomic, and proteomic analyses revealed a role of the PRPF8/Brr2 regulation in 5’-splice site (5’SS) selection by spliceosomes, for which disruption impaired alternative splicing and weak/suboptimal 5’SS selection, and enhanced cryptic splicing, predominantly in ciliary and retinal-specific transcripts. Altered splicing efficiency, nuclear speckles organisation, and PRPF8 interaction with U6 snRNA, caused accumulation of active spliceosomes and poly(A)+ mRNAs in unique splicing clusters located at the nuclear periphery of photoreceptors. Collectively these elucidate the role of PRPF8/Brr2 regulatory mechanisms in splicing and the molecular basis of retinal disease, informing therapeutic approaches.
Probing the tunable multi-cone band structure in Bernal bilayer graphene
Authors: Seiler Anna M. , Jacobsen Nils , Statz Martin , Fernandez Noelia , Falorsi Francesca , Watanabe Kenji , Taniguchi Takashi , Dong Zhiyu , Levitov Leonid S. , Weitz R. Thomas
Published: April 2024

Bernal bilayer graphene (BLG) offers a highly flexible platform for tuning the band structure, featuring two distinct regimes. One is a tunable band gap induced by large displacement fields. Another is a gapless metallic band occurring at low fields, featuring rich fine structure consisting of four linearly dispersing Dirac cones and van Hove singularities. Even though BLG has been extensively studied experimentally, the evidence of this band structure is still elusive, likely due to insufficient energy resolution. Here, we use Landau levels as markers of the energy dispersion and analyze the Landau level spectrum in a regime where the cyclotron orbits of electrons or holes in momentum space are small enough to resolve the distinct mini Dirac cones. We identify the presence of four Dirac cones and map out topological transitions induced by displacement field. By clarifying the low-energy properties of BLG bands, these findings provide a valuable addition to the toolkit for graphene electronics.
A hippocampus-accumbens code guides goal-directed appetitive behavior
Authors: Barnstedt Oliver , Mocellin Petra , Remy Stefan
Published: April 2024

The dorsal hippocampus (dHPC) is a key brain region for the expression of spatial memories, such as navigating towards a learned reward location. The nucleus accumbens (NAc) is a prominent projection target of dHPC and implicated in value-based action selection. Yet, the contents of the dHPC→NAc information stream and their acute role in behavior remain largely unknown. Here, we found that optogenetic stimulation of the dHPC→NAc pathway while mice navigated towards a learned reward location was both necessary and sufficient for spatial memory-related appetitive behaviors. To understand the task-relevant coding properties of individual NAc-projecting hippocampal neurons (dHPC→NAc), we used in vivo dual-color two-photon imaging. In contrast to other dHPC neurons, the dHPC→NAc subpopulation contained more place cells, with enriched spatial tuning properties. This subpopulation also showed enhanced coding of non-spatial task-relevant behaviors such as deceleration and appetitive licking. A generalized linear model revealed enhanced conjunctive coding in dHPC→NAc neurons which improved the identification of the reward zone. We propose that dHPC routes specific reward-related spatial and behavioral state information to guide NAc action selection.
A facile one step route that introduces functionality to polymer powders for laser sintering
Authors: Krumins Eduards , Crawford Liam A. , Rogers David M. , Machado Fabricio , Taresco Vincenzo , East Mark , Irving Samuel H. , Fowler Harriet R. , Jiang Long , Starr Nichola , Parmenter Christopher D. J. , Kortsen Kristoffer , Cuzzucoli Crucitti Valentina , Avery Simon V. , Tuck Christopher J. , Howdle Steven M.
Published: April 2024

Laser Sintering (LS) is a type of Additive Manufacturing (AM) exploiting laser processing of polymeric particles to produce 3D objects. Because of its ease of processability and thermo-physical properties, polyamide-12 (PA-12) represents ~95% of the polymeric materials used in LS. This constrains the functionality of the items produced, including limited available colours. Moreover, PA-12 objects tend to biofoul in wet environments. Therefore, a key challenge is to develop an inexpensive route to introduce desirable functionality to PA-12. We report a facile, clean, and scalable approach to modification of PA-12, exploiting supercritical carbon dioxide (scCO2) and free radical polymerizations to yield functionalised PA-12 materials. These can be easily printed using commercial apparatus. We demonstrate the potential by creating coloured PA-12 materials and show that the same approach can be utilized to create anti-biofouling objects. Our approach to functionalise materials could open significant new applications for AM.
Epidemiological, clinical, and genomic landscape of coccidioidomycosis in northeastern Brazil
Authors: Eulálio Kelsen Dantas , Kollath Daniel R. , Martins Liline Maria Soares , Filho Antonio de Deus , Cavalcanti Maria do Amparo Salmito , Moreira Lucas Machado , Tenório Bernardo Guerra , Alves Lucas Gomes de Brito , Yamauchi Danielle , Barrozo Ligia Vizeu , Thompson III George R. , Nacher Mathieu , Stajich Jason E. , Benard Gil , Bagagli Eduardo , Felipe Maria Sueli Soares , Barker Bridget M. , Trilles Luciana , Teixeira Marcus de Melo
Published: April 2024

Coccidioidomycosis, listed as a priority mycosis by the WHO, is endemic in the United States but often overlooked in Central and South America. Employing a multi-institutional approach, we investigate how disease characteristics, pathogen genetic variation, and environmental factors impact coccidioidomycosis epidemiology and outcomes in South America. We identified 292 cases (1978–2021) and 42 outbreaks in Piauí and Maranhão states, Brazil, the largest series outside the US/Mexico epidemic zone. The male-to-female ratio was 57.4:1 and the most common activity was armadillo hunting (91.1%) 4 to 30 days before symptom onset. Most patients (92.8%) exhibited typical acute pulmonary disease, with cough (93%), fever (90%), and chest pain (77%) as predominant symptoms. The case fatality rate was 8%. Our negative binomial regression model indicates that reduced precipitation levels in the current (p = 0.015) and preceding year (p = 0.001) predict heightened incidence. Unlike other hotspots, acidic soil characterizes this region. Brazilian strains differ genomically from other C. posadasii lineages. Northeastern Brazil presents a distinctive coccidioidomycosis profile, with armadillo hunters facing elevated risks. Low annual rainfall emerges as a key factor in increasing cases. A unique C. posadasii lineage in Brazil suggests potential differences in environmental, virulence, and/or pathogenesis traits compared to other Coccidioides genotypes.
Annelid adult cell type diversity and their pluripotent cellular origins
Authors: Álvarez-Campos Patricia , García-Castro Helena , Emili Elena , Pérez-Posada Alberto , del Olmo Irene , Peron Sophie , Salamanca-Díaz David A. , Mason Vincent , Metzger Bria , Bely Alexandra E. , Kenny Nathan J. , Özpolat B. Duygu , Solana Jordi
Published: April 2024

Many annelids can regenerate missing body parts or reproduce asexually, generating all cell types in adult stages. However, the putative adult stem cell populations involved in these processes, and the diversity of cell types generated by them, are still unknown. To address this, we recover 75,218 single cell transcriptomes of the highly regenerative and asexually-reproducing annelid Pristina leidyi. Our results uncover a rich cell type diversity including annelid specific types as well as novel types. Moreover, we characterise transcription factors and gene networks that are expressed specifically in these populations. Finally, we uncover a broadly abundant cluster of putative stem cells with a pluripotent signature. This population expresses well-known stem cell markers such as vasa, piwi and nanos homologues, but also shows heterogeneous expression of differentiated cell markers and their transcription factors. We find conserved expression of pluripotency regulators, including multiple chromatin remodelling and epigenetic factors, in piwi+ cells. Finally, lineage reconstruction analyses reveal computational differentiation trajectories from piwi+ cells to diverse adult types. Our data reveal the cell type diversity of adult annelids by single cell transcriptomics and suggest that a piwi+ cell population with a pluripotent stem cell signature is associated with adult cell type differentiation.
Systematic investigation of chemo-immunotherapy synergism to shift anti-PD-1 resistance in cancer
Authors: Wang Yue , Pattarayan Dhamotharan , Huang Haozhe , Zhao Yueshan , Li Sihan , Wang Yifei , Zhang Min , Li Song , Yang Da
Published: April 2024

Chemo-immunotherapy combinations have been regarded as one of the most practical ways to improve immunotherapy response in cancer patients. In this study, we integrate the transcriptomics data from anti-PD-1-treated tumors and compound-treated cancer cell lines to systematically screen for chemo-immunotherapy synergisms in silico. Through analyzing anti-PD-1 induced expression changes in patient tumors, we develop a shift ability score to measure if a chemotherapy or a small molecule inhibitor treatment can shift anti-PD-1 resistance in tumor cells. By applying shift ability analysis to 41,321 compounds and 16,853 shRNA treated cancer cell lines transcriptomic data, we characterize the landscape of chemo-immunotherapy synergism and experimentally validated a mitochondrial RNA-dependent mechanism for drug-induced immune activation in tumor. Our study represents an effort to mechanistically characterize chemo-immunotherapy synergism and will facilitate future pre-clinical and clinical studies.
Enhanced atmospheric oxidation toward carbon neutrality reduces methane’s climate forcing
Authors: Liu Mingxu , Song Yu , Matsui Hitoshi , Shang Fang , Kang Ling , Cai Xuhui , Zhang Hongsheng , Zhu Tong
Published: April 2024

The hydroxyl radical (OH), as the central atmospheric oxidant, controls the removal rates of methane, a powerful greenhouse gas. It is being suggested that OH levels would decrease with reductions of nitrogen oxides and ozone levels by climate polices, but this remains unsettled. Here, we show that driven by the carbon neutrality pledge, the global-mean OH concentration, derived from multiple chemistry-climate model simulations, is projected to be significantly increasing with a trend of 0.071‒0.16% per year during 2015–2100. The leading cause of this OH enhancement is dramatic decreases in carbon monoxide and methane concentrations, which together reduce OH sinks. The OH increase shortens methane’s lifetime by 0.19‒1.1 years across models and subsequently diminishes methane’s radiative forcing. If following a largely unmitigated scenario, the global OH exhibits a significant decrease that would exacerbate methane’s radiative forcing. Thus, we highlight that targeted emission abatement strategies for sustained oxidation capacity can benefit climate change mitigation in the Anthropocene.
Spatiotemporal immune atlas of a clinical-grade gene-edited pig-to-human kidney xenotransplant
Authors: Cheung Matthew D. , Asiimwe Rebecca , Erman Elise N. , Fucile Christopher F. , Liu Shanrun , Sun Chiao-Wang , Hanumanthu Vidya Sagar , Pal Harish C. , Wright Emma D. , Ghajar-Rahimi Gelare , Epstein Daniel , Orandi Babak J. , Kumar Vineeta , Anderson Douglas J. , Greene Morgan E. , Bell Markayla , Yates Stefani , Moore Kyle H. , LaFontaine Jennifer , Killian John T. , Baker Gavin , Perry Jackson , Khan Zayd , Reed Rhiannon , Little Shawn C. , Rosenberg Alexander F. , George James F. , Locke Jayme E. , Porrett Paige M.
Published: April 2024

Pig-to-human xenotransplantation is rapidly approaching the clinical arena; however, it is unclear which immunomodulatory regimens will effectively control human immune responses to pig xenografts. Here, we transplant a gene-edited pig kidney into a brain-dead human recipient on pharmacologic immunosuppression and study the human immune response to the xenograft using spatial transcriptomics and single-cell RNA sequencing. Human immune cells are uncommon in the porcine kidney cortex early after xenotransplantation and consist of primarily myeloid cells. Both the porcine resident macrophages and human infiltrating macrophages express genes consistent with an alternatively activated, anti-inflammatory phenotype. No significant infiltration of human B or T cells into the porcine kidney xenograft is detectable. Altogether, these findings provide proof of concept that conventional pharmacologic immunosuppression may be able to restrict infiltration of human immune cells into the xenograft early after compatible pig-to-human kidney xenotransplantation.
Splice modulators target PMS1 to reduce somatic expansion of the Huntington’s disease-associated CAG repeat
Authors: McLean Zachariah L. , Gao Dadi , Correia Kevin , Roy Jennie C. L. , Shibata Shota , Farnum Iris N. , Valdepenas-Mellor Zoe , Kovalenko Marina , Rapuru Manasa , Morini Elisabetta , Ruliera Jayla , Gillis Tammy , Lucente Diane , Kleinstiver Benjamin P. , Lee Jong-Min , MacDonald Marcy E. , Wheeler Vanessa C. , Mouro Pinto Ricardo , Gusella James F.
Published: April 2024

Huntington’s disease (HD) is a dominant neurological disorder caused by an expanded HTT exon 1 CAG repeat that lengthens huntingtin’s polyglutamine tract. Lowering mutant huntingtin has been proposed for treating HD, but genetic modifiers implicate somatic CAG repeat expansion as the driver of onset. We find that branaplam and risdiplam, small molecule splice modulators that lower huntingtin by promoting HTT pseudoexon inclusion, also decrease expansion of an unstable HTT exon 1 CAG repeat in an engineered cell model. Targeted CRISPR-Cas9 editing shows this effect is not due to huntingtin lowering, pointing instead to pseudoexon inclusion in PMS1. Homozygous but not heterozygous inactivation of PMS1 also reduces CAG repeat expansion, supporting PMS1 as a genetic modifier of HD and a potential target for therapeutic intervention. Although splice modulation provides one strategy, genome-wide transcriptomics also emphasize consideration of cell-type specific effects and polymorphic variation at both target and off-target sites.
A hemoprotein with a zinc-mirror heme site ties heme availability to carbon metabolism in cyanobacteria
Authors: Grosjean Nicolas , Yee Estella F. , Kumaran Desigan , Chopra Kriti , Abernathy Macon , Biswas Sandeep , Byrnes James , Kreitler Dale F. , Cheng Jan-Fang , Ghosh Agnidipta , Almo Steven C. , Iwai Masakazu , Niyogi Krishna K. , Pakrasi Himadri B. , Sarangi Ritimukta , van Dam Hubertus , Yang Lin , Blaby Ian K. , Blaby-Haas Crysten E.
Published: April 2024

Heme has a critical role in the chemical framework of the cell as an essential protein cofactor and signaling molecule that controls diverse processes and molecular interactions. Using a phylogenomics-based approach and complementary structural techniques, we identify a family of dimeric hemoproteins comprising a domain of unknown function DUF2470. The heme iron is axially coordinated by two zinc-bound histidine residues, forming a distinct two-fold symmetric zinc-histidine-iron-histidine-zinc site. Together with structure-guided in vitro and in vivo experiments, we further demonstrate the existence of a functional link between heme binding by Dri1 (Domain related to iron 1, formerly ssr1698) and post-translational regulation of succinate dehydrogenase in the cyanobacterium Synechocystis, suggesting an iron-dependent regulatory link between photosynthesis and respiration. Given the ubiquity of proteins containing homologous domains and connections to heme metabolism across eukaryotes and prokaryotes, we propose that DRI (Domain Related to Iron; formerly DUF2470) functions at the molecular level as a heme-dependent regulatory domain.
CoPoP liposomes displaying stabilized clade C HIV-1 Env elicit tier 2 multiclade neutralization in rabbits
Authors: Koornneef Annemart , Vanshylla Kanika , Hardenberg Gijs , Rutten Lucy , Strokappe Nika M. , Tolboom Jeroen , Vreugdenhil Jessica , Boer Karin Feddes-de , Perkasa Aditya , Blokland Sven , Burger Judith A. , Huang Wei-Chiao , Lovell Jonathan F. , van Manen Danielle , Sanders Rogier W. , Zahn Roland C. , Schuitemaker Hanneke , Langedijk Johannes P. M. , Wegmann Frank
Published: April 2024

One of the strategies towards an effective HIV-1 vaccine is to elicit broadly neutralizing antibody responses that target the high HIV-1 Env diversity. Here, we present an HIV-1 vaccine candidate that consists of cobalt porphyrin-phospholipid (CoPoP) liposomes decorated with repaired and stabilized clade C HIV-1 Env trimers in a prefusion conformation. These particles exhibit high HIV-1 Env trimer decoration, serum stability and bind broadly neutralizing antibodies. Three sequential immunizations of female rabbits with CoPoP liposomes displaying a different clade C HIV-1 gp140 trimer at each dosing generate high HIV-1 Env-specific antibody responses. Additionally, serum neutralization is detectable against 18 of 20 multiclade tier 2 HIV-1 strains. Furthermore, the peak antibody titers induced by CoPoP liposomes can be recalled by subsequent heterologous immunization with Ad26-encoded membrane-bound stabilized Env antigens. Hence, a CoPoP liposome-based HIV-1 vaccine that can generate cross-clade neutralizing antibody immunity could potentially be a component of an efficacious HIV-1 vaccine.
Multiplicative joint coding in preparatory activity for reaching sequence in macaque motor cortex
Authors: Wang Tianwei , Chen Yun , Zhang Yiheng , Cui He
Published: April 2024

Although the motor cortex has been found to be modulated by sensory or cognitive sequences, the linkage between multiple movement elements and sequence-related responses is not yet understood. Here, we recorded neuronal activity from the motor cortex with implanted micro-electrode arrays and single electrodes while monkeys performed a double-reach task that was instructed by simultaneously presented memorized cues. We found that there existed a substantial multiplicative component jointly tuned to impending and subsequent reaches during preparation, then the coding mechanism transferred to an additive manner during execution. This multiplicative joint coding, which also spontaneously emerged in recurrent neural networks trained for double reach, enriches neural patterns for sequential movement, and might explain the linear readout of elemental movements.
Reciprocating RNA Polymerase batters through roadblocks
Authors: Qian Jin , Cartee Allison , Xu Wenxuan , Yan Yan , Wang Bing , Artsimovitch Irina , Dunlap David , Finzi Laura
Published: April 2024

RNA polymerases must transit through protein roadblocks to produce full-length transcripts. Here we report real-time measurements of Escherichia coli RNA polymerase passing through different barriers. As intuitively expected, assisting forces facilitated, and opposing forces hindered, RNA polymerase passage through lac repressor protein bound to natural binding sites. Force-dependent differences were significant at magnitudes as low as 0.2 pN and were abolished in the presence of the transcript cleavage factor GreA, which rescues backtracked RNA polymerase. In stark contrast, opposing forces promoted passage when the rate of RNA polymerase backtracking was comparable to, or faster than the rate of dissociation of the roadblock, particularly in the presence of GreA. Our experiments and simulations indicate that RNA polymerase may transit after roadblocks dissociate, or undergo cycles of backtracking, recovery, and ramming into roadblocks to pass through. We propose that such reciprocating motion also enables RNA polymerase to break protein-DNA contacts that hold RNA polymerase back during promoter escape and RNA chain elongation. This may facilitate productive transcription in vivo.
The deepwater oxygen deficit in stratified shallow seas is mediated by diapycnal mixing
Authors: Rippeth Tom , Shen Sijing , Lincoln Ben , Scannell Brian , Meng Xin , Hopkins Joanne , Sharples Jonathan
Published: April 2024

Seasonally stratified shelf seas are amongst the most biologically productive on the planet. A consequence is that the deeper waters can become oxygen deficient in late summer. Predictions suggest global warming will accelerate this deficiency. Here we integrate turbulence timeseries with vertical profiles of water column properties from a seasonal stratified shelf sea to estimate oxygen and biogeochemical fluxes. The profiles reveal a significant subsurface chlorophyll maximum and associated mid-water oxygen maximum. We show that the oxygen maximum supports both upward and downwards O2 fluxes. The upward flux is into the surface mixed layer, whilst the downward flux into the deep water will partially off-set the seasonal O2 deficit. The results indicate the fluxes are sensitive to both the water column structure and mixing rates implying the development of the seasonal O2 deficit is mediated by diapcynal mixing. Analysis of current shear indicate that the downward flux is supported by tidal mixing, whilst the upwards flux is dominated by wind driven near-inertial shear. Summer storminess therefore plays an important role in the development of the seasonal deep water O2 deficit.
Metavalently bonded tellurides: the essence of improved thermoelectric performance in elemental Te
Authors: An Decheng , Zhang Senhao , Zhai Xin , Yang Wutao , Wu Riga , Zhang Huaide , Fan Wenhao , Wang Wenxian , Chen Shaoping , Cojocaru-Mirédin Oana , Zhang Xian-Ming , Wuttig Matthias , Yu Yuan
Published: April 2024

Elemental Te is important for semiconductor applications including thermoelectric energy conversion. Introducing dopants such as As, Sb, and Bi has been proven critical for improving its thermoelectric performance. However, the remarkably low solubility of these elements in Te raises questions about the mechanism with which these dopants can improve the thermoelectric properties. Indeed, these dopants overwhelmingly form precipitates rather than dissolve in the Te lattice. To distinguish the role of doping and precipitation on the properties, we have developed a correlative method to locally determine the structure-property relationship for an individual matrix or precipitate. We reveal that the conspicuous enhancement of electrical conductivity and power factor of bulk Te stems from the dopant-induced metavalently bonded telluride precipitates. These precipitates form electrically beneficial interfaces with the Te matrix. A quantum-mechanical-derived map uncovers more candidates for advancing Te thermoelectrics. This unconventional doping scenario adds another recipe to the design options for thermoelectrics and opens interesting pathways for microstructure design.
The rule of four: anomalous distributions in the stoichiometries of inorganic compounds
Authors: Gazzarrini Elena , Cersonsky Rose K. , Bercx Marnik , Adorf Carl S. , Marzari Nicola
Published: April 2024

Why are materials with specific characteristics more abundant than others? This is a fundamental question in materials science and one that is traditionally difficult to tackle, given the vastness of compositional and configurational space. We highlight here the anomalous abundance of inorganic compounds whose primitive unit cell contains a number of atoms that is a multiple of four. This occurrence—named here the rule of four—has to our knowledge not previously been reported or studied. Here, we first highlight the rule’s existence, especially notable when restricting oneself to experimentally known compounds, and explore its possible relationship with established descriptors of crystal structures, from symmetries to energies. We then investigate this relative abundance by looking at structural descriptors, both of global (packing configurations) and local (the smooth overlap of atomic positions) nature. Contrary to intuition, the overabundance does not correlate with low-energy or high-symmetry structures; in fact, structures which obey the rule of four are characterized by low symmetries and loosely packed arrangements maximizing the free volume. We are able to correlate this abundance with local structural symmetries, and visualize the results using a hybrid supervised-unsupervised machine learning method.
Computed entropy spectra for grain boundary segregation in polycrystals
Authors: Tuchinda Nutth , Schuh Christopher A.
Published: April 2024

Grain boundary solute segregation influences most bulk material properties, and understanding solute thermodynamics at grain boundaries is critical for engineering them. However, the vast grain boundary space in polycrystals is challenging to evaluate due to its size, especially for the intrinsically hard-to-compute segregation excess entropy. Here data science methods are used to generate a database of site-wise grain boundary segregation entropy spectra for 155 dilute binary alloys within the harmonic approximation. The spectral framework allows scale bridging between the calculated atomistic site-wise energy-entropy spectra and macroscopic segregation entropy estimates. The results affirm that macroscopic averaging is not sufficient: a spectral treatment of grain boundary segregation is needed to accurately model bulk temperature dependence of grain boundary solute segregation. The calculated spectral entropy database and thermodynamic framework can be applied for both understanding segregation experiments and alloy design exercises, paving the way to a finite-temperature grain boundary genome.
JWST detection of a supernova associated with GRB 221009A without an r-process signature
Authors: Blanchard Peter K. , Villar V. Ashley , Chornock Ryan , Laskar Tanmoy , Li Yijia , Leja Joel , Pierel Justin , Berger Edo , Margutti Raffaella , Alexander Kate D. , Barnes Jennifer , Cendes Yvette , Eftekhari Tarraneh , Kasen Daniel , LeBaron Natalie , Metzger Brian D. , Muzerolle Page James , Rest Armin , Sears Huei , Siegel Daniel M. , Yadavalli S. Karthik
Published: April 2024

Identifying the sites of r-process nucleosynthesis, a primary mechanism of heavy element production, is a key goal of astrophysics. The discovery of the brightest gamma-ray burst (GRB) to date, GRB 221009A, presented an opportunity to spectroscopically test the idea that r-process elements are produced following the collapse of rapidly rotating massive stars. Here we present James Webb Space Telescope observations of GRB 221009A obtained +168 and +170 rest-frame days after the gamma-ray trigger, and demonstrate that they are well described by a SN 1998bw-like supernova (SN) and power-law afterglow, with no evidence for a component from r-process emission. The SN, with a nickel mass of approximately 0.09 M⊙, is only slightly fainter than the brightness of SN 1998bw at this phase, which indicates that the SN is not an unusual GRB-SN. This demonstrates that the GRB and SN mechanisms are decoupled and that highly energetic GRBs are not likely to produce significant quantities of r-process material, which leaves open the question of whether explosions of massive stars are key sources of r-process elements. Moreover, the host galaxy of GRB 221009A has a very low metallicity of approximately 0.12 Z⊙ and strong H2 emission at the explosion site, which is consistent with recent star formation, hinting that environmental factors are responsible for its extreme energetics.
Magnetic origin of the discrepancy between stellar limb-darkening models and observations
Authors: Kostogryz Nadiia M. , Shapiro Alexander I. , Witzke Veronika , Cameron Robert H. , Gizon Laurent , Krivova Natalie A. , Ludwig Hans-G. , Maxted Pierre F. L. , Seager Sara , Solanki Sami K. , Valenti Jeff
Published: April 2024

Stars appear darker at their limbs than at their disk centres because at the limb we are viewing the higher and cooler layers of stellar photospheres. Yet, limb darkening derived from state-of-the-art stellar atmosphere models systematically fails to reproduce recent transiting exoplanet light curves from the Kepler, TESS and JWST telescopes—stellar brightness obtained from measurements drops less steeply towards the limb than predicted by models. Previous models assumed stellar atmospheres devoid of magnetic fields. Here we use stellar atmosphere models computed with the three-dimensional radiative magnetohydrodynamic code MURaM to show that a small-scale concentration of magnetic fields on the stellar surface affects limb darkening at a level that allows us to explain the observations. Our findings provide a way forward to improve the determination of exoplanet radii and especially the transmission spectroscopy analysis for transiting planets, which relies on a very accurate description of stellar limb darkening from the visible to the infrared. Furthermore, our findings imply that limb darkening allows estimates of the small-scale magnetic field strength on stars with transiting planets.
Homogenized gridded dataset for drought and hydrometeorological modeling for the continental United States
Authors: Erhardt Robert , Di Vittorio Courtney A. , Hepler Staci A. , Lowman Lauren E. L. , Wei Wendy
Published: April 2024

We present a novel data set for drought in the continental US (CONUS) built to enable computationally efficient spatio-temporal statistical and probabilistic models of drought. We converted drought data obtained from the widely-used US Drought Monitor (USDM) from its native geo-referenced polygon format to a 0.5 degree regular grid. We merged known environmental drivers of drought, including those obtained from the North American Land Data Assimilation System (NLDAS-2), US Geological Survey (USGS) streamflow data, and National Oceanic and Atmospheric Administration (NOAA) teleconnections data. The resulting data set permits statistical and probabilistic modeling of drought with explicit spatial and/or temporal dependence. Such models could be used to forecast drought at short-range, seasonal to sub-seasonal, and inter-annual timescales with uncertainty, extending the reach and value of the current US Drought Outlook from the National Weather Service Climate Prediction Center. This novel data product provides the first common gridded dataset that includes critical variables used to inform hydrological and meteorological drought.
New ridge parameter estimators for the quasi-Poisson ridge regression model
Authors: Shahzad Aamir , Amin Muhammad , Emam Walid , Faisal Muhammad
Published: April 2024

The quasi-Poisson regression model is used for count data and is preferred over the Poisson regression model in the case of over-dispersed count data. The quasi-likelihood estimator is used to estimate the regression coefficients of the quasi-Poisson regression model. The quasi-likelihood estimator gives sub-optimal estimates if regressors are highly correlated—multicollinearity issue. Biased estimation methods are often used to overcome the multicollinearity issue in the regression model. In this study, we explore the ridge estimator for the quasi-Poisson regression model to mitigate the multicollinearity issue. Furthermore, we propose various ridge parameter estimators for this model. We derive the theoretical properties of the ridge estimator and compare its performance with the quasi-likelihood estimator in terms of matrix and scalar mean squared error. We further compared the proposed estimator numerically through a Monte Carlo simulation study and a real-life application. We found that both the simulation and application results show the superiority of the ridge estimator, particularly with the best ridge parameter estimator, over the quasi-likelihood estimator in the presence of multicollinearity issue.
The importance of continents, oceans and plate tectonics for the evolution of complex life: implications for finding extraterrestrial civilizations
Authors: Stern Robert J. , Gerya Taras V.
Published: April 2024

Within the uncertainties of involved astronomical and biological parameters, the Drake Equation typically predicts that there should be many exoplanets in our galaxy hosting active, communicative civilizations (ACCs). These optimistic calculations are however not supported by evidence, which is often referred to as the Fermi Paradox. Here, we elaborate on this long-standing enigma by showing the importance of planetary tectonic style for biological evolution. We summarize growing evidence that a prolonged transition from Mesoproterozoic active single lid tectonics (1.6 to 1.0 Ga) to modern plate tectonics occurred in the Neoproterozoic Era (1.0 to 0.541 Ga), which dramatically accelerated emergence and evolution of complex species. We further suggest that both continents and oceans are required for ACCs because early evolution of simple life must happen in water but late evolution of advanced life capable of creating technology must happen on land. We resolve the Fermi Paradox (1) by adding two additional terms to the Drake Equation: foc(the fraction of habitable exoplanets with significant continents and oceans) and fpt(the fraction of habitable exoplanets with significant continents and oceans that have had plate tectonics operating for at least 0.5 Ga); and (2) by demonstrating that the product of focand fptis very small (< 0.00003–0.002). We propose that the lack of evidence for ACCs reflects the scarcity of long-lived plate tectonics and/or continents and oceans on exoplanets with primitive life.
Tuning spatially fractionated radiotherapy dose profiles using the moiré effect
Authors: Reaz Fardous , Traneus Erik , Bassler Niels
Published: April 2024

Spatially Fractionated Radiotherapy (SFRT) has demonstrated promising potential in cancer treatment, combining the advantages of reduced post-radiation effects and enhanced local control rates. Within this paradigm, proton minibeam radiotherapy (pMBRT) was suggested as a new treatment modality, possibly producing superior normal tissue sparing to conventional proton therapy, leading to improvements in patient outcomes. However, an effective and convenient beam generation method for pMBRT, capable of implementing various optimum dose profiles, is essential for its real-world application. Our study investigates the potential of utilizing the moiré effect in a dual collimator system (DCS) to generate pMBRT dose profiles with the flexibility to modify the center-to-center distance (CTC) of the dose distribution in a technically simple way.

We employ the Geant4 Monte Carlo simulations tool to demonstrate that the angle between the two collimators of a DCS can significantly impact the dose profile. Varying the DCS angle from 10$$^{\circ }$$

∘

to 50$$^{\circ }$$

∘

we could cover CTC ranging from 11.8 mm to 2.4 mm, respectively. Further investigations reveal the substantial influence of the multi-slit collimator’s (MSC) physical parameters on the spatially fractionated dose profile, such as period (CTC), throughput, and spacing between MSCs. These findings highlight opportunities for precision dose profile adjustments tailored to specific clinical scenarios.

The DCS capacity for rapid angle adjustments during the energy transition stages of a spot scanning system can facilitate dynamic alterations in the irradiation profile, enhancing dose contrast in normal tissues. Furthermore, its unique attribute of spatially fractionated doses in both lateral directions could potentially improve normal tissue sparing by minimizing irradiated volume. Beyond the realm of pMBRT, the dual MSC system exhibits remarkable versatility, showing compatibility with different types of beams (X-rays and electrons) and applicability across various SFRT modalities.

Our study illuminates the dual MSC system’s potential as an efficient and adaptable tool in the refinement of pMBRT techniques. By enabling meticulous control over irradiation profiles, this system may expedite advancements in clinical and experimental applications, thereby contributing to the evolution of SFRT strategies.
Fast learning without synaptic plasticity in spiking neural networks
Authors: Subramoney Anand , Bellec Guillaume , Scherr Franz , Legenstein Robert , Maass Wolfgang
Published: April 2024

Spiking neural networks are of high current interest, both from the perspective of modelling neural networks of the brain and for porting their fast learning capability and energy efficiency into neuromorphic hardware. But so far we have not been able to reproduce fast learning capabilities of the brain in spiking neural networks. Biological data suggest that a synergy of synaptic plasticity on a slow time scale with network dynamics on a faster time scale is responsible for fast learning capabilities of the brain. We show here that a suitable orchestration of this synergy between synaptic plasticity and network dynamics does in fact reproduce fast learning capabilities of generic recurrent networks of spiking neurons. This points to the important role of recurrent connections in spiking networks, since these are necessary for enabling salient network dynamics. We show more specifically that the proposed synergy enables synaptic weights to encode more general information such as priors and task structures, since moment-to-moment processing of new information can be delegated to the network dynamics.
Increased anger and stress and heightened connectivity between IFG and vmPFC in victims during social interaction
Authors: Röhr Ann-Kristin , Kohn Nils , Bergs Rene , Clemens Benjamin , Lampert Angelika , Spehr Marc , Habel Ute , Wagels Lisa
Published: April 2024

Self-identification as a victim of violence may lead to increased negative emotions and stress and thus, may change both structure and function of the underlying neural network(s). In a trans-diagnostic sample of individuals who identified themselves as victims of violence and a matched control group with no prior exposure to violence, we employed a social exclusion paradigm, the Cyberball task, to stimulate the re-experience of stress. Participants were partially excluded in the ball-tossing game without prior knowledge. We analyzed group differences in brain activity and functional connectivity during exclusion versus inclusion in exclusion-related regions. The victim group showed increased anger and stress levels during all conditions. Activation patterns during the task did not differ between groups but an enhanced functional connectivity between the IFG and the right vmPFC distinguished victims from controls during exclusion. This effect was driven by aberrant connectivity in victims during inclusion rather than exclusion, indicating that victimization affects emotional responses and inclusion-related brain connectivity rather than exclusion-related brain activity or connectivity. Victims may respond differently to the social context itself. Enhanced negative emotions and connectivity deviations during social inclusion may depict altered social processing and may thus affect social interactions.
Impact of different storage conditions with combined use of ethylene blocker on ‘Shalimar’ apple variety
Authors: Khera Kartik , Büchele Felix , Wood Rachael Maree , Thewes Fabio Rodrigo , Wagner Roger , Hagemann Michael Helmut , Neuwald Daniel Alexandre
Published: April 2024

This research investigates the impact of storage conditions on the quality and preservation of 'Shalimar' apples, a relatively new cultivar known for its resistance to apple scab and powdery mildew. The study explores the efficacy of different storage techniques such as regular atmosphere (RA), controlled atmosphere (CA), and dynamic controlled atmosphere with CO2 Monitoring (DCA-CD), as well as the integration of 1-methylcyclopropene (1-MCP) at different storage temperatures (1 °C and 3 °C). Various fruit quality parameters were monitored under different storage conditions, including firmness, titratable acidity, total soluble solids, background color, respiration, ethylene production, and volatile compounds. The results indicate that the controlled atmosphere (CA) at 1 °C emerges as an efficient method for long-term storage. However, it is noted that CA storage may impact the apple aroma, emphasizing the need for a balance between preservation and consumer acceptability. On the other hand, DCA-CD at variable temperatures (approximately 2.5 °C) offers a promising approach for maintaining fruit quality and a higher concentration of volatile compounds. Integrating 1-MCP enhances firmness, but its impact varies across storage conditions. Principal component analysis (PCA) provides insights into the relationships between storage conditions, fruit quality, and volatile compounds. This study contributes valuable insights into optimizing storage strategies for ‘Shalimar’ apples, addressing sustainability and quality preservation in apple production.
Lethal and sublethal heat-exposure of bed bugs (Cimex lectularius L.) causes alarm pheromone emission and elicits a movement response in nearby recipients
Authors: Ashbrook Aaron R. , Feder Jeffrey L. , Bennett Gary W. , Ginzel Matthew D. , Gondhalekar Ameya D.
Published: April 2024

Many gregarious insect species use aggregation and alarm pheromones. The bed bug, Cimex lectularius L., emits an alarm pheromone (AP), a 70/30 blend of (E)-2-hexenal and (E)-2-octenal, when threatened. Bed bugs avoid temperatures above 43 °C, which are lethal to bugs and used commercially as spatial heat treatments to manage infestations. However, the interaction of bed bug AP in heat avoidance has not been investigated. The goal of this research was to: 1) determine if bed bugs emit AP as an alarm response to heat exposure, and 2) quantify the behavioral responses of conspecifics to AP emitted by heat-exposed bed bugs. Using a selected ion flow tube mass spectrometer, we found that bed bugs responded to lethal and sublethal heat exposure by emitting AP. The Harlan laboratory population emitted more pheromone than a laboratory adapted field population from Florida (McCall). Harlan females emitted the most AP, followed by Harlan males, McCall females and males. In separate behavioral experiments, we showed that conspecifics (i.e., recipients) reacted to AP released by heat exposed bed bugs (i.e., emitters) by frantically moving within 50 mm and 100 mm test arenas. The Harlan recipients reacted to AP in 100 mm areas, whereas the McCall strain did not, indicating a short area of effectiveness of the AP. Synthetic AP components tested in behavioral experiments caused identical effects as the natural AP blend released by heat-exposed bed bugs.
The polymorphism analysis for CD36 among platelet donors
Authors: Lyu Qilu , Lin Yuwei , Pan Yiming , Guan Xiaoyu , Ji Xin , Peng Mozhen , Li Qian , Wang Zhijang , Zhang Zhihui , Luo Zhen , Su Pincan , Wang Jue
Published: April 2024

CD36 may defect on platelets and/or monocytes in healthy individuals, which was defined as CD36 deficiency. However, we did not know the correlation between the molecular and protein levels completely. Here, we aim to determine the polymorphisms of the CD36 gene, RNA level, and CD36 on platelets and in plasma. The individuals were sequenced by Sanger sequencing. Bioinformational analysis was used by the HotMuSiC, CUPSAT, SAAFEC-SEQ, and FoldX. RNA analysis and CD36 protein detection were performed by qPCR, flow cytometry, and ELISA. In this study, we found c.1228_1239delATTGTGCCTATT (allele frequency = 0.0072) with the highest frequency among our cohort, and one mutation (c.1329_1354dupGATAGAAATGATCTTACTCAGTGTTG) was not present in the dbSNP database. 5 mutations located in the extracellular domain sequencing region with confirmation in deficient individuals, of which c.284T>C, c.512A>G, c.572C>T, and c.869T>C were found to have a deleterious impact on CD36 protein stability. Furthermore, the MFI of CD36 expression on platelets in the mutation-carry, deleterious-effect, and deficiency group was significantly lower than the no-mutation group (P < 0.0500). In addition, sCD36 levels in type II individuals were significantly lower compared with positive controls (P = 0.0060). Nevertheless, we found the presence of sCD36 in a type I individual. RNA analysis showed CD36 RNA levels in platelets of type II individuals were significantly lower than the positive individuals (P = 0.0065). However, no significant difference was observed in monocytes (P = 0.7500). We identified the most prevalent mutation (c.1228_1239delATTGTGCCTATT) among Kunming donors. Besides, our results suggested RNA level alterations could potentially underlie type II deficiency. Furthermore, sCD36 may hold promise for assessing immune reaction risk in CD36-deficient individuals, but more studies should be conducted to validate this hypothesis.
Differential responses of rumen and fecal fermentation and microbiota of Liaoning cashmere goats after 2-hydroxy-4-(methylthio) butanoic acid isopropyl ester supplementation
Authors: Zhong Zhiqiang , Sun Peiyuan , Zhang Yuning , Li Lingyun , Han Di , Pan Xiaoguang , Zhang Ruiyang
Published: April 2024

The 2-hydroxy-4-(methylthio) butanoic acid isopropyl ester (HMBi), a rumen protective methionine, has been extensively studied in dairy cows and beef cattle and has been shown to regulate gastrointestinal microbiota and improve production performance. However, knowledge of the application of HMBi on cashmere goats and the simultaneous study of rumen and hindgut microbiota is still limited. In this study, HMBi supplementation increased the concentration of total serum protein, the production of microbial protein in the rumen and feces, as well as butyrate production in the feces. The results of PCoA and PERMANOVA showed no significant difference between the rumen microbiota, but there was a dramatic difference between the fecal microbiota of the two groups of Cashmere goats after the HMBi supplementation. Specifically, in the rumen, HMBi significantly increased the relative abundance of some fiber-degrading bacteria (such as Fibrobacter) compared with the CON group. In the feces, as well as a similar effect as in the rumen (increasing the relative abundance of some fiber-degrading bacteria, such as Lachnospiraceae FCS020 group and ASV32), HMBi diets also increased the proliferation of butyrate-producing bacteria (including Oscillospiraceae UCG-005 and Christensenellaceae R-7 group). Overall, these results demonstrated that HMBi could regulate the rumen and fecal microbial composition of Liaoning cashmere goats and benefit the host.