bluuebunny/crossref_metadata_2025_split huggingface dataset:
The broad impact of cell death genes on the human disease phenome
Authors: Rich Abigail L. , Lin Phillip , Gamazon Eric R. , Zinkel Sandra S. 
Published: April 2024

AbstractCell death mediated by genetically defined signaling pathways influences the health and dynamics of all tissues, however the tissue specificity of cell death pathways and the relationships between these pathways and human disease are not well understood. We analyzed the expression profiles of an array of 44 cell death genes involved in apoptosis, necroptosis, and pyroptosis cell death pathways across 49 human tissues from GTEx, to elucidate the landscape of cell death gene expression across human tissues, and the relationship between tissue-specific genetically determined expression and the human phenome. We uncovered unique cell death gene expression profiles across tissue types, suggesting there are physiologically distinct cell death programs in different tissues. Using summary statistics-based transcriptome wide association studies (TWAS) on human traits in the UK Biobank (n ~ 500,000), we evaluated 513 traits encompassing ICD-10 defined diagnoses and laboratory-derived traits. Our analysis revealed hundreds of significant (FDR < 0.05) associations between genetically regulated cell death gene expression and an array of human phenotypes encompassing both clinical diagnoses and hematologic parameters, which were independently validated in another large-scale DNA biobank (BioVU) at Vanderbilt University Medical Center (n = 94,474) with matching phenotypes. Cell death genes were highly enriched for significant associations with blood traits versus non-cell-death genes, with apoptosis-associated genes enriched for leukocyte and platelet traits. Our findings are also concordant with independently published studies (e.g. associations between BCL2L11/BIM expression and platelet & lymphocyte counts). Overall, these results suggest that cell death genes play distinct roles in their contribution to human phenotypes, and that cell death genes influence a diverse array of human traits.
A live attenuated vaccine to prevent severe neonatal Escherichia coli K1 infections
Authors: Sereme Youssouf , Schrimp Cécile , Faury Helène , Agapoff Maeva , Lefebvre-Wloszczowski Esther , Chang Marchand Yunhua , Ageron-Ardila Elisabeth , Panafieu Emilie , Blec Frank , Coureuil Mathieu , Frapy Eric , Tsatsaris Vassilis , Bonacorsi Stephane , Skurnik David 
Published: April 2024

AbstractPreterm birth is currently the leading cause of neonatal morbidity and mortality. Genetic, immunological and infectious causes are suspected. Preterm infants have a higher risk of severe bacterial neonatal infections, most of which are caused by Escherichia coli an in particular E. coli K1strains. Women with history of preterm delivery have a high risk of recurrence and therefore constitute a target population for the development of vaccine against E. coli neonatal infections. Here, we characterize the immunological, microbiological and protective properties of a live attenuated vaccine candidate in adult female mice and their pups against after a challenge by K1 and non-K1 strains of E. coli. Our results show that the E. coli K1 E11 ∆aroA vaccine induces strong immunity, driven by polyclonal bactericidal antibodies. In our model of meningitis, mothers immunized prior to mating transfer maternal antibodies to pups, which protect newborn mice against various K1 and non-K1 strains of E. coli. Given the very high mortality rate and the neurological sequalae associated with neonatal E. coli K1 meningitis, our results constitute preclinical proof of concept for the development of a live attenuated vaccine against severe E. coli infections in women at risk of preterm delivery.
Engineering an artificial catch bond using mechanical anisotropy
Authors: Liu Zhaowei , Liu Haipei , Vera Andrés M. , Yang Byeongseon , Tinnefeld Philip , Nash Michael A. 
Published: April 2024

AbstractCatch bonds are a rare class of protein-protein interactions where the bond lifetime increases under an external pulling force. Here, we report how modification of anchor geometry generates catch bonding behavior for the mechanostable Dockerin G:Cohesin E (DocG:CohE) adhesion complex found on human gut bacteria. Using AFM single-molecule force spectroscopy in combination with bioorthogonal click chemistry, we mechanically dissociate the complex using five precisely controlled anchor geometries. When tension is applied between residue #13 on CohE and the N-terminus of DocG, the complex behaves as a two-state catch bond, while in all other tested pulling geometries, including the native configuration, it behaves as a slip bond. We use a kinetic Monte Carlo model with experimentally derived parameters to simulate rupture force and lifetime distributions, achieving strong agreement with experiments. Single-molecule FRET measurements further demonstrate that the complex does not exhibit dual binding mode behavior at equilibrium but unbinds along multiple pathways under force. Together, these results show how mechanical anisotropy and anchor point selection can be used to engineer artificial catch bonds.
Large-volume focus control at 10 MHz refresh rate via fast line-scanning amplitude-encoded scattering-assisted holography
Authors: Shibukawa Atsushi , Higuchi Ryota , Song Gookho , Mikami Hideharu , Sudo Yuki , Jang Mooseok 
Published: April 2024

AbstractThe capability of focus control has been central to optical technologies that require both high temporal and spatial resolutions. However, existing varifocal lens schemes are commonly limited to the response time on the microsecond timescale and share the fundamental trade-off between the response time and the tuning power. Here, we propose an ultrafast holographic focusing method enabled by translating the speed of a fast 1D beam scanner into the speed of the complex wavefront modulation of a relatively slow 2D spatial light modulator. Using a pair of a digital micromirror device and a resonant scanner, we demonstrate an unprecedented refresh rate of focus control of 31 MHz, which is more than 1,000 times faster than the switching rate of a digital micromirror device. We also show that multiple micrometer-sized focal spots can be independently addressed in a range of over 1 MHz within a large volume of 5 mm × 5 mm × 5.5 mm, validating the superior spatiotemporal characteristics of the proposed technique – high temporal and spatial precision, high tuning power, and random accessibility in a three-dimensional space. The demonstrated scheme offers a new route towards three-dimensional light manipulation in the 100 MHz regime.
Optics miniaturization strategy for demanding Raman spectroscopy applications
Authors: Ilchenko Oleksii , Pilhun Yurii , Kutsyk Andrii , Slobodianiuk Denys , Goksel Yaman , Dumont Elodie , Vaut Lukas , Mazzoni Chiara , Morelli Lidia , Boisen Sofus , Stergiou Konstantinos , Aulin Yaroslav , Rindzevicius Tomas , Andersen Thomas Emil , Lassen Mikael , Mundhada Hemanshu , Jendresen Christian Bille , Philipsen Peter Alshede , Hædersdal Merete , Boisen Anja 
Published: April 2024

AbstractRaman spectroscopy provides non-destructive, label-free quantitative studies of chemical compositions at the microscale as used on NASA’s Perseverance rover on Mars. Such capabilities come at the cost of high requirements for instrumentation. Here we present a centimeter-scale miniaturization of a Raman spectrometer using cheap non-stabilized laser diodes, densely packed optics, and non-cooled small sensors. The performance is comparable with expensive bulky research-grade Raman systems. It has excellent sensitivity, low power consumption, perfect wavenumber, intensity calibration, and 7 cm−1resolution within the 400–4000 cm−1range using a built-in reference. High performance and versatility are demonstrated in use cases including quantification of methanol in beverages, in-vivo Raman measurements of human skin, fermentation monitoring, chemical Raman mapping at sub-micrometer resolution, quantitative SERS mapping of the anti-cancer drug methotrexate and in-vitro bacteria identification. We foresee that the miniaturization will allow realization of super-compact Raman spectrometers for integration in smartphones and medical devices, democratizing Raman technology.
Metabolic plasticity, essentiality and therapeutic potential of ribose-5-phosphate synthesis in Toxoplasma gondii
Authors: Guo Xuefang , Ji Nuo , Guo Qinghong , Wang Mengting , Du Huiyu , Pan Jiajia , Xiao Lihua , Gupta Nishith , Feng Yaoyu , Xia Ningbo 
Published: April 2024

AbstractRibose-5-phosphate (R5P) is a precursor for nucleic acid biogenesis; however, the importance and homeostasis of R5P in the intracellular parasite Toxoplasma gondii remain enigmatic. Here, we show that the cytoplasmic sedoheptulose-1,7-bisphosphatase (SBPase) is dispensable. Still, its co-deletion with transaldolase (TAL) impairs the double mutant’s growth and increases 13C-glucose-derived flux into pentose sugars via the transketolase (TKT) enzyme. Deletion of the latter protein affects the parasite’s fitness but is not lethal and is correlated with an increased carbon flux via the oxidative pentose phosphate pathway. Further, loss of TKT leads to a decline in 13C incorporation into glycolysis and the TCA cycle, resulting in a decrease in ATP levels and the inability of phosphoribosyl-pyrophosphate synthetase (PRPS) to convert R5P into 5′-phosphoribosyl-pyrophosphate and thereby contribute to the production of AMP and IMP. Likewise, PRPS is essential for the lytic cycle. Not least, we show that RuPE-mediated metabolic compensation is imperative for the survival of the ΔsbpaseΔtal strain. In conclusion, we demonstrate that multiple routes can flexibly supply R5P to enable parasite growth and identify catalysis by TKT and PRPS as critical enzymatic steps. Our work provides novel biological and therapeutic insights into the network design principles of intracellular parasitism in a clinically-relevant pathogen.
Comparative characterization of the infant gut microbiome and their maternal lineage by a multi-omics approach
Authors: Barker-Tejeda Tomás Clive , Zubeldia-Varela Elisa , Macías-Camero Andrea , Alonso Lola , Martín-Antoniano Isabel Adoración , Rey-Stolle María Fernanda , Mera-Berriatua Leticia , Bazire Raphaëlle , Cabrera-Freitag Paula , Shanmuganathan Meera , Britz-McKibbin Philip , Ubeda Carles , Francino M. Pilar , Barber Domingo , Ibáñez-Sandín María Dolores , Barbas Coral , Pérez-Gordo Marina , Villaseñor Alma 
Published: April 2024

AbstractThe human gut microbiome establishes and matures during infancy, and dysregulation at this stage may lead to pathologies later in life. We conducted a multi-omics study comprising three generations of family members to investigate the early development of the gut microbiota. Fecal samples from 200 individuals, including infants (0-12 months old; 55% females, 45% males) and their respective mothers and grandmothers, were analyzed using two independent metabolomics platforms and metagenomics. For metabolomics, gas chromatography and capillary electrophoresis coupled to mass spectrometry were applied. For metagenomics, both 16S rRNA gene and shotgun sequencing were performed. Here we show that infants greatly vary from their elders in fecal microbiota populations, function, and metabolome. Infants have a less diverse microbiota than adults and present differences in several metabolite classes, such as short- and branched-chain fatty acids, which are associated with shifts in bacterial populations. These findings provide innovative biochemical insights into the shaping of the gut microbiome within the same generational line that could be beneficial in improving childhood health outcomes.
Single-cell multiomics reveals the interplay of clonal evolution and cellular plasticity in hepatoblastoma
Authors: Roehrig Amélie , Hirsch Theo Z. , Pire Aurore , Morcrette Guillaume , Gupta Barkha , Marcaillou Charles , Imbeaud Sandrine , Chardot Christophe , Gonzales Emmanuel , Jacquemin Emmanuel , Sekiguchi Masahiro , Takita Junko , Nagae Genta , Hiyama Eiso , Guérin Florent , Fabre Monique , Aerts Isabelle , Taque Sophie , Laithier Véronique , Branchereau Sophie , Guettier Catherine , Brugières Laurence , Fresneau Brice , Zucman-Rossi Jessica , Letouzé Eric 
Published: April 2024

AbstractHepatoblastomas (HB) display heterogeneous cellular phenotypes that influence the clinical outcome, but the underlying mechanisms are poorly understood. Here, we use a single-cell multiomic strategy to unravel the molecular determinants of this plasticity. We identify a continuum of HB cell states between hepatocytic (scH), liver progenitor (scLP) and mesenchymal (scM) differentiation poles, with an intermediate scH/LP population bordering scLP and scH areas in spatial transcriptomics. Chromatin accessibility landscapes reveal the gene regulatory networks of each differentiation pole, and the sequence of transcription factor activations underlying cell state transitions. Single-cell mapping of somatic alterations reveals the clonal architecture of each tumor, showing that each genetic subclone displays its own range of cellular plasticity across differentiation states. The most scLP subclones, overexpressing stem cell and DNA repair genes, proliferate faster after neo-adjuvant chemotherapy. These results highlight how the interplay of clonal evolution and epigenetic plasticity shapes the potential of HB subclones to respond to chemotherapy.
Thermodiffusive desalination
Authors: Xu Shuqi , Hutchinson Alice J. , Taheri Mahdiar , Corry Ben , Torres Juan F. 
Published: April 2024

AbstractDesalination could solve the grand challenge of water scarcity, but materials-based and conventional thermal desalination methods generally suffer from scaling, fouling and materials degradation. Here, we propose and assess thermodiffusive desalination (TDD), a method that operates entirely in the liquid phase and notably excludes evaporation, freezing, membranes, or ion-adsorbing materials. Thermodiffusion is the migration of species under a temperature gradient and can be driven by thermal energy ubiquitous in the environment. Experimentally, a 450 ppm concentration drop was achieved by thermodiffusive separation when passing a NaCl/H2O solution through a single channel. This was further increased through re-circulation as a proof of concept for TDD. We also demonstrate via molecular dynamics and experiments that TDD in multi-component seawater is more amenable than in binary NaCl/H2O solutions. Numerically, we show that a scalable cascaded channel structure can further amplify thermodiffusive separation, achieving a concentration drop of 25000 ppm with a recovery rate of 10%. The minimum electric power consumption in this setup can be as low as 3 Whe m−3, which is only 1% of the theoretical minimum energy for desalination. TDD has potential in areas with abundant thermal energy but limited electrical power resources and can contribute to alleviating global freshwater scarcity.
Multicore fiber optic imaging reveals that astrocyte calcium activity in the mouse cerebral cortex is modulated by internal motivational state
Authors: Gau Yung-Tian A. , Hsu Eric T. , Cha Richard J. , Pak Rebecca W. , Looger Loren L. , Kang Jin U. , Bergles Dwight E. 
Published: April 2024

AbstractAstrocytes are a direct target of neuromodulators and can influence neuronal activity on broad spatial and temporal scales in response to a rise in cytosolic calcium. However, our knowledge about how astrocytes are recruited during different animal behaviors remains limited. To measure astrocyte activity calcium in vivo during normative behaviors, we utilize a high-resolution, long working distance multicore fiber optic imaging system that allows visualization of individual astrocyte calcium transients in the cerebral cortex of freely moving mice. We define the spatiotemporal dynamics of astrocyte calcium changes during diverse behaviors, ranging from sleep-wake cycles to the exploration of novel objects, showing that their activity is more variable and less synchronous than apparent in head-immobilized imaging conditions. In accordance with their molecular diversity, individual astrocytes often exhibit distinct thresholds and activity patterns during explorative behaviors, allowing temporal encoding across the astrocyte network. Astrocyte calcium events were induced by noradrenergic and cholinergic systems and modulated by internal state. The distinct activity patterns exhibited by astrocytes provides a means to vary their neuromodulatory influence in different behavioral contexts and internal states.
A chromosomal-scale genome assembly of modern cultivated hybrid sugarcane provides insights into origination and evolution
Authors: Bao Yixue , Zhang Qing , Huang Jiangfeng , Zhang Shengcheng , Yao Wei , Yu Zehuai , Deng Zuhu , Yu Jiaxin , Kong Weilong , Yu Xikai , Lu Shan , Wang Yibin , Li Ru , Song Yuhan , Zou Chengwu , Xu Yuzhi , Liu Zongling , Yu Fan , Song Jiaming , Huang Youzong , Zhang Jisen , Wang Haifeng , Chen Baoshan , Zhang Xingtan , Zhang Muqing 
Published: April 2024

AbstractSugarcane is a vital crop with significant economic and industrial value. However, the cultivated sugarcane’s ultra-complex genome still needs to be resolved due to its high ploidy and extensive recombination between the two subgenomes. Here, we generate a chromosomal-scale, haplotype-resolved genome assembly for a hybrid sugarcane cultivar ZZ1. This assembly contains 10.4 Gb genomic sequences and 68,509 annotated genes with defined alleles in two sub-genomes distributed in 99 original and 15 recombined chromosomes. RNA-seq data analysis shows that sugar accumulation-associated gene families have been primarily expanded from the ZZSO subgenome. However, genes responding to pokkah boeng disease susceptibility have been derived dominantly from the ZZSS subgenome. The region harboring the possible smut resistance genes has expanded significantly. Among them, the expansion of WAK and FLS2 families is proposed to have occurred during the breeding of ZZ1. Our findings provide insights into the complex genome of hybrid sugarcane cultivars and pave the way for future genomics and molecular breeding studies in sugarcane.
Spin-orbit coupling induced Van Hove singularity in proximity to a Lifshitz transition in Sr4Ru3O10
Authors: Marques Carolina A. , Murgatroyd Philip A. E. , Fittipaldi Rosalba , Osmolska Weronika , Edwards Brendan , Benedičič Izidor , Siemann Gesa-R. , Rhodes Luke C. , Buchberger Sebastian , Naritsuka Masahiro , Abarca-Morales Edgar , Halliday Daniel , Polley Craig , Leandersson Mats , Horio Masafumi , Chang Johan , Arumugam Raja , Lettieri Mariateresa , Granata Veronica , Vecchione Antonio , King Phil D. C. , Wahl Peter 
Published: April 2024

AbstractVan Hove singularities (VHss) in the vicinity of the Fermi energy often play a dramatic role in the physics of strongly correlated electron materials. The divergence of the density of states generated by VHss can trigger the emergence of phases such as superconductivity, ferromagnetism, metamagnetism, and density wave orders. A detailed understanding of the electronic structure of these VHss is therefore essential for an accurate description of such instabilities. Here, we study the low-energy electronic structure of the trilayer strontium ruthenate Sr4Ru3O10, identifying a rich hierarchy of VHss using angle-resolved photoemission spectroscopy and millikelvin scanning tunneling microscopy. Comparison of k-resolved electron spectroscopy and quasiparticle interference allows us to determine the structure of the VHss and demonstrate the crucial role of spin-orbit coupling in shaping them. We use this to develop a minimal model from which we identify a mechanism for driving a field-induced Lifshitz transition in ferromagnetic metals.
Temperature optima of a natural diatom population increases as global warming proceeds
Authors: Hattich G. S. I. , Jokinen S. , Sildever S. , Gareis M. , Heikkinen J. , Junghardt N. , Segovia M. , Machado M. , Sjöqvist C. 
Published: April 2024

AbstractStudies in laboratory-based experimental evolution have demonstrated that phytoplankton species can rapidly adapt to higher temperatures. However, adaptation processes and their pace remain largely unknown under natural conditions. Here, by comparing resurrected Skeletonema marinoi strains from the Baltic Sea during the past 60 years, we show that modern S. marinoi have increased their temperature optima by 1 °C. With the increasing ability to grow in higher temperatures, growth rates in cold water decreased. Modern S. marinoi modified their valve:girdle ratio under warmer temperatures, which probably increases nutrient uptake ability. This was supported by the upregulation of several genes related to nitrate metabolism in modern strains grown under high temperatures. Our approach using resurrected strains demonstrates the adaptation potential of naturally occurring marine diatoms to increasing temperatures as global warming proceeds and exemplifies a realistic pace of evolution, which is an order of magnitude slower than estimated by experimental evolution.
Spike sorting with Kilosort4
Authors: Pachitariu Marius , Sridhar Shashwat , Pennington Jacob , Stringer Carsen 
Published: April 2024

AbstractSpike sorting is the computational process of extracting the firing times of single neurons from recordings of local electrical fields. This is an important but hard problem in neuroscience, made complicated by the nonstationarity of the recordings and the dense overlap in electrical fields between nearby neurons. To address the spike-sorting problem, we have been openly developing the Kilosort framework. Here we describe the various algorithmic steps introduced in different versions of Kilosort. We also report the development of Kilosort4, a version with substantially improved performance due to clustering algorithms inspired by graph-based approaches. To test the performance of Kilosort, we developed a realistic simulation framework that uses densely sampled electrical fields from real experiments to generate nonstationary spike waveforms and realistic noise. We found that nearly all versions of Kilosort outperformed other algorithms on a variety of simulated conditions and that Kilosort4 performed best in all cases, correctly identifying even neurons with low amplitudes and small spatial extents in high drift conditions.
Ancient DNA indicates a century of overhunting did not reduce genetic diversity in Pacific Walruses (Odobenus rosmarus divergens)
Authors: Mills Kendall K. , Hildebrandt Kyndall P. B. , Everson Kathryn M. , Horstmann Lara , Misarti Nicole , Olson Link E. 
Published: April 2024

AbstractPacific Walruses (Odobenus rosmarus divergens [Illiger 1815]) are gregarious marine mammals considered to be sentinels of the Arctic because of their dependence on sea ice for feeding, molting, and parturition. Like many other marine mammal species, their population sizes were decimated by historical overhunting in the nineteenth and twentieth centuries. Although they have since been protected from nearly all commercial hunting pressure, they now face rapidly accelerating habitat loss as global warming reduces the extent of summer sea ice in the Arctic. To investigate how genetic variation was impacted by overhunting, we obtained mitochondrial DNA sequences from historic Pacific Walrus samples in Alaska that predate the period of overhunting, as well as from extant populations. We found that genetic variation was unchanged over this period, suggesting Pacific Walruses are resilient to genetic attrition in response to reduced population size, and that this may be related to their high vagility and lack of population structure. Although Pacific Walruses will almost certainly continue to decline in number as the planet warms and summer sea ice is further reduced, they may be less susceptible to the ratcheting effects of inbreeding that typically accompany shrinking populations.