bluuebunny/crossref_metadata_2025 huggingface dataset:
Darwin in India: Anticolonial Evolutionism at the Dawn of the Twentieth Century
Authors: Marwah Inder S.
Published: February 2023

This article examines how Indian anticolonialists drew on Darwinism and evolutionary theory to resist British imperialism at the turn of the twentieth century. Drawing on archival material fromThe Bengalee(and beyond), I show how Indian nationalists marshaled evolutionist schemas to contest stage-based accounts of social advancement rationalizing despotic rule in India. I argue that Darwinian evolutionism enabled anticolonialists to respond to a particular decolonial dilemma—that of developmentalism, the unilinear notion of historical time justifying India’s political subjection. While Darwinism’s social application is commonly understood to sustain imperialism, I demonstrate that it served, in the colonial context, to deconstruct historicist tropes portraying India as politically immature. Drawing on evolutionism, nationalists contested the presumptions of imperialist discourse and reconceptualized progress in novel, anticolonial terms. Darwin’s travel to India thus exposes a distinctive decolonial quandary, the syncretic Indian anticolonial response to it, and the intractability of the contradictions facing decolonizing movements globally.
A nonparametric analysis of climate change nexus on agricultural productivity in Africa: implications on food security
Authors: Bernard Boima M. , Song Yanping , Narcisse Mulinga , Hena Sehresh , Wang Xin
Published: February 2023

Earlier research largely ignored the effects of climate change on the growth of agricultural total factor productivity (TFP) in Africa. This study shows how climate inputs impact TFP growth in addition to other productivity growth indicators and metrics, as well as how they can impact overall input efficiency as productivity drivers. We use a panel of 42 African nations from 1999 to 2019 and a nonparametric data envelopment analysis-Malmquist technique. The non-parametric analysis revealed that the average growth rate of the non-climate-induced TFP estimates was 1.9%, while the average growth rate of the climate-induced TFP estimates was 2.4%. Accounting for temperature and precipitation separately, TFP grew by 2.3% on average. This growth rate (2.3%) is slightly less than the combined effect of temperature and precipitation (2.4%) but higher than the typical TFP growth rate (1.9%) that ignores climate variables, indicating that TFP growth in African agriculture risks being underestimated when climate inputs are ignored. We also find the distribution of the climate effects to vary across regions. In northern Africa, for example, the temperature-induced TFP growth rates were negative due to rising temperature in the region. Evidence from the decomposed TFP estimates indicates that climate variables also influence productivity determinants. However, technology improvement is fundamental to mitigating the effects of extreme weather inputs on TFP growth in Africa's agriculture. As a result, a few policy suggestions are provided to help policymakers deal with the effects of climate change on TFP growth in Africa's agriculture and ensure food security. The study advocated for a reevaluation of the climate–agriculture effect in order to fully comprehend the role of climate factors and their contributions to agricultural TFP growth in Africa.
NOx‐Induced Changes in Upper Tropospheric O3 During the Asian Summer Monsoon in Present‐Day and Future Climate
Authors: Roy Chaitri , Rathod Sagar D. , Ayantika D. C.
Published: February 2023

The upper tropospheric ozone (O3) strongly influences the atmosphere's radiative budget. Using the Aerosol and Chemistry Model Intercomparison Project simulations, we study the influence of present‐day and future anthropogenic nitrogen oxides (NOx) emissions on the upper tropospheric O3 concentrations over India during the Asian summer monsoon (ASM). We observe that the upper tropospheric O3 concentrations increased 1.5 times over the ASM anticyclone region during the ASM due to higher NOx emissions in 2014 compared to 1850, and their transport due to convection. These NOx‐induced O3 changes exert a regional positive radiative forcing of 0.6 Wm−2 at the top of the atmosphere. The upper tropospheric O3 increases in the future with increasing NOx emissions. However, air quality policies to reduce surface NOx emissions also reduce the upper tropospheric O3 over India during the ASM.
Rheological Heterogeneities Control the Non‐Progressive Uplift of the Young Iranian Plateau
Authors: Gao Yifan , Chen Ling , Yang Jianfeng , Wang Kun
Published: February 2023

The Iranian plateau is at the early stage of plateau development and intracontinental deformation in response to the Arabia‐Eurasia collision. Its compressive deformation is concentrated in the northern plateau but skips the central counterpart, challenging the common views envisaging the progressive uplift from the collisional front to the hinterland. Based on three‐dimensional, crustal‐scale numerical models, we present how the rheological heterogeneities common in continents control the deformation of the young Iranian plateau. The weak northern plateau ensures itself a preferential zone in accommodating continental collision. The N‐S strike‐slip faults within the non‐rigid central plateau, formed along the boundaries between the tectonic units with rheological contrast, suppress the shortening of the central plateau while further accentuating the compressive deformation of the northern plateau. Our results suggest a non‐progressive intracontinental deformation pattern where rheological boundaries and mechanically weak zones, not necessarily those close to collisional fronts, preferentially accommodate continental convergence.
The Mini Induced Magnetospheres at Mars
Authors: Dubinin E. , Fraenz M. , Pätzold M. , Tellmann S. , DiBraccio G. , McFadden J.
Published: February 2023

We report on observations made by the Mars Atmosphere and Volatile EvolutioN spacecraft at Mars, in the region of the ion plume. We observe that in some cases, when the number density of oxygen ions is comparable to the density of the solar wind protons interaction between both plasmas leads to formation in the magnetosheath of mini induced magnetospheres possessing all typical features of induced magnetospheres typically observed at Mars or Venus: a pileup of the magnetic field at the head of the ion cloud, magnetospheric cavity, partially void of solar wind protons, draping of the interplanetary magnetic field around the mini obstacle, formation of a magnetic tail with a current sheet, in which protons are accelerated by the magnetic field tensions. These new observations may shed a light on the mechanism of formation of induced magnetospheres.
Mantle Phase Changes Detected From Stochastic Tomography
Authors: Cormier Vernon F. , Lithgow‐Bertelloni Carolina , Stixrude Lars , Zheng Yingcai
Published: February 2023

Stochastic tomography, made possible by dense deployments of seismic sensors, is used to identify phase changes in Earth's mantle that occur over depth intervals. This technique inverts spatial coherences of amplitudes and travel times of body waves to determine the depth and dependence of the spatial spectrum of seismic velocity. This spectrum is interpreted using the predicted thermodynamic stability of mineral composition and phase as a function of temperature and pressure, in which the metamorphic temperature derivative of seismic velocities is used as a proxy for the effects of heterogeneity induced in a region undergoing a phase change. Peaks in the temperature derivative of seismic velocity closely match those found from applying stochastic tomography to elements of Earthscope and Flex arrays. Within ±12 km, peaks in the fluctuation of P velocity at 425, 500, and 600 km depth beneath the western US agree with those predicted by a mechanical mixture of harzburgite and basalt, 180 K cooler than a 1600 K adiabat in the mantle transition zone. A broad peak at 250 km depth may be associated with chemical heterogeneity induced by dehydration of subducted oceanic sediments, and a peak at 775 km depth with a phase change in subducted basalt. Non‐detection of predicted phase changes less than 10 km in width is consistent with the resolution possible with the seismic arrays used in the inversion, including the sharp endothermic phase change near 660 km. These interpretations are consistent with the known history of plate subduction beneath North America.
Enhanced Linkage of Summer Drought in Southern China to the North Pacific Oscillation Since 2000
Authors: Hu Yuepeng , Zhou Botao , Han Tingting , Li Huixin
Published: February 2023

Based on the standardized precipitation evaporation index and reanalysis data, this article reveals that the relationship between the North Pacific Oscillation (NPO) and the drought over southern China in summer shifts from an insignificant correlation to a significant negative correlation after 2000. During the significant period (2001–2018), the positive NPO phase corresponds to an anomalous anticyclonic circulation dominating the mid‐low latitude North Pacific, which suppresses the moisture transport into southern China. Meanwhile, the easterly anomalies south of the anomalous anticyclonic circulation prevailing in the equatorial Pacific are coupled with a cooling of sea surface temperature in the central tropical Pacific, which enhances the Walker circulation and further induces an anomalous meridional circulation with the descending anomalies over southern China. Such moisture and dynamical conditions favor the occurrence of drought in southern China. During the former period (1983–2000), however, the NPO‐related atmospheric circulations over the North Pacific shift northward. In this case, the NPO shows insignificant relations with the moisture and dynamical conditions over southern China, thereby diluting the linkage of the NPO to the drought in southern China. The interdecadal strengthening in the relationship between the NPO and above atmospheric conditions is attributed to the westward (southward) extension of the NPO northern (southern) center. The larger interannual variability of spring sea ice in the Bering Sea and the southward movement of summer storm track over the North Pacific are hypothesized to account for the expansion of the NPO structure.
Study of the inflammatory activating process in the early stage of Fusobacterium nucleatum infected PDLSCs
Authors: Wang Yushang , Wang Lihua , Sun Tianyong , Shen Song , Li Zixuan , Ma Xiaomei , Gu Xiufeng , Zhang Xiumei , Peng Ai , Xu Xin , Feng Qiang
Published: February 2023

Fusobacterium nucleatum(F. nucleatum) is an early pathogenic colonizer in periodontitis, but the host response to infection with this pathogen remains unclear. In this study, we built anF. nucleatuminfectious model with human periodontal ligament stem cells (PDLSCs) and showed thatF. nucleatumcould inhibit proliferation, and facilitate apoptosis, ferroptosis, and inflammatory cytokine production in a dose-dependent manner. TheF. nucleatumadhesin FadA acted as a proinflammatory virulence factor and increased the expression of interleukin(IL)-1β, IL-6 and IL-8. Further study showed that FadA could bind with PEBP1 to activate the Raf1-MAPK and IKK-NF-κB signaling pathways. Time-course RNA-sequencing analyses showed the cascade of gene activation process in PDLSCs with increasing durations ofF. nucleatuminfection. NFκB1 and NFκB2 upregulated after 3 h ofF. nucleatum-infection, and the inflammatory-related genes in the NF-κB signaling pathway were serially elevated with time. Using computational drug repositioning analysis, we predicted and validated that two potential drugs (piperlongumine and fisetin) could attenuate the negative effects ofF. nucleatum-infection. Collectively, this study unveils the potential pathogenic mechanisms ofF. nucleatumand the host inflammatory response at the early stage ofF. nucleatuminfection.
Parameter estimation of the structured illumination pattern based on principal component analysis (PCA): PCA-SIM
Authors: Chen Xin , Hou Yiwei , Xi Peng
Published: February 2023

Principal component analysis (PCA), a common dimensionality reduction method, is introduced into SIM to identify the frequency vectors and pattern phases of the illumination pattern with precise subpixel accuracy, fast speed, and noise-robustness, which is promising for real-time and long-term live-cell imaging.
Ecophysiology and genomics of the brackish water adapted SAR11 subclade IIIa
Authors: Lanclos V Celeste , Rasmussen Anna N , Kojima Conner Y , Cheng Chuankai , Henson Michael W , Faircloth Brant C , Francis Christopher A , Thrash J Cameron
Published: February 2023

The Order Pelagibacterales (SAR11) is the most abundant group of heterotrophic bacterioplankton in global oceans and comprises multiple subclades with unique spatiotemporal distributions. Subclade IIIa is the primary SAR11 group in brackish waters and shares a common ancestor with the dominant freshwater IIIb (LD12) subclade. Despite its dominance in brackish environments, subclade IIIa lacks systematic genomic or ecological studies. Here, we combine closed genomes from new IIIa isolates, new IIIa MAGS from San Francisco Bay (SFB), and 460 highly complete publicly available SAR11 genomes for the most comprehensive pangenomic study of subclade IIIa to date. Subclade IIIa represents a taxonomic family containing three genera (denoted as subgroups IIIa.1, IIIa.2, and IIIa.3) that had distinct ecological distributions related to salinity. The expansion of taxon selection within subclade IIIa also established previously noted metabolic differentiation in subclade IIIa compared to other SAR11 subclades such as glycine/serine prototrophy, mosaic glyoxylate shunt presence, and polyhydroxyalkanoate synthesis potential. Our analysis further shows metabolic flexibility among subgroups within IIIa. Additionally, we find that subclade IIIa.3 bridges the marine and freshwater clades based on its potential for compatible solute transport, iron utilization, and bicarbonate management potential. Pure culture experimentation validated differential salinity ranges in IIIa.1 and IIIa.3 and provided detailed IIIa cell size and volume data. This study is an important step forward for understanding the genomic, ecological, and physiological differentiation of subclade IIIa and the overall evolutionary history of SAR11.
Somatic mutations can induce a noninflamed tumour microenvironment via their original gene functions, despite deriving neoantigens
Authors: Ishino Takamasa , Kawashima Shusuke , Tanji Etsuko , Ueno Toshihide , Ueda Youki , Ogasawara Sadahisa , Sato Kazuhito , Mano Hiroyuki , Ishihara Soichiro , Kato Naoya , Kawazu Masahito , Togashi Yosuke
Published: February 2023

Background

Identifying biomarkers to predict immune checkpoint inhibitor (ICI) efficacy is warranted. Considering that somatic mutation-derived neoantigens induce strong immune responses, patients with a high tumour mutational burden reportedly tend to respond to ICIs. However, there are several conflicting data. Therefore, we focused on the original function of neoantigenic mutations and their impact on the tumour microenvironment (TME).

Methods

We evaluated 88 high-frequency microsatellite instability (MSI-H) colorectal cancers and analysed the function of the identified neoantigenic mutations and their influence on programmed cell death 1 (PD-1) blockade efficacy. The results were validated using The Cancer Genome Atlas (TCGA) datasets.

Results

We identified frameshift mutations in RNF43 as a common neoantigenic gene mutation in MSI-H tumours. However, loss-of-function RNF43 mutations induced noninflamed TME by activating the WNT/β-catenin signalling pathway. In addition, loss of RNF43 function induced resistance to PD-1 blockade even in neoantigen-rich tumours. TCGA dataset analyses demonstrated that passenger rather than driver gene mutations were related to the inflamed TME in diverse cancer types.

Conclusions

We propose a novel concept of “paradoxical neoantigenic mutations” that can induce noninflamed TME through their original gene functions, despite deriving neoantigens, suggesting the significance of qualities as well as quantities in neoantigenic mutations.
A high-fidelity quantum matter-link between ion-trap microchip modules
Authors: Akhtar M. , Bonus F. , Lebrun-Gallagher F. R. , Johnson N. I. , Siegele-Brown M. , Hong S. , Hile S. J. , Kulmiya S. A. , Weidt S. , Hensinger W. K.
Published: February 2023

System scalability is fundamental for large-scale quantum computers (QCs) and is being pursued over a variety of hardware platforms. For QCs based on trapped ions, architectures such as the quantum charge-coupled device (QCCD) are used to scale the number of qubits on a single device. However, the number of ions that can be hosted on a single quantum computing module is limited by the size of the chip being used. Therefore, a modular approach is of critical importance and requires quantum connections between individual modules. Here, we present the demonstration of a quantum matter-link in which ion qubits are transferred between adjacent QC modules. Ion transport between adjacent modules is realised at a rate of 2424 s−1 and with an infidelity associated with ion loss during transport below 7 × 10−8. Furthermore, we show that the link does not measurably impact the phase coherence of the qubit. The quantum matter-link constitutes a practical mechanism for the interconnection of QCCD devices. Our work will facilitate the implementation of modular QCs capable of fault-tolerant utility-scale quantum computation.
Spatially non-uniform condensates emerge from dynamically arrested phase separation
Authors: Erkamp Nadia A. , Sneideris Tomas , Ausserwöger Hannes , Qian Daoyuan , Qamar Seema , Nixon-Abell Jonathon , St George-Hyslop Peter , Schmit Jeremy D. , Weitz David A. , Knowles Tuomas P. J.
Published: February 2023

The formation of biomolecular condensates through phase separation from proteins and nucleic acids is emerging as a spatial organisational principle used broadly by living cells. Many such biomolecular condensates are not, however, homogeneous fluids, but possess an internal structure consisting of distinct sub-compartments with different compositions. Notably, condensates can contain compartments that are depleted in the biopolymers that make up the condensate. Here, we show that such double-emulsion condensates emerge via dynamically arrested phase transitions. The combination of a change in composition coupled with a slow response to this change can lead to the nucleation of biopolymer-poor droplets within the polymer-rich condensate phase. Our findings demonstrate that condensates with a complex internal architecture can arise from kinetic, rather than purely thermodynamic driving forces, and provide more generally an avenue to understand and control the internal structure of condensates in vitro and in vivo.
Parallelized multidimensional analytic framework applied to mammary epithelial cells uncovers regulatory principles in EMT
Authors: Paul Indranil , Bolzan Dante , Youssef Ahmed , Gagnon Keith A. , Hook Heather , Karemore Gopal , Oliphant Michael U. J. , Lin Weiwei , Liu Qian , Phanse Sadhna , White Carl , Padhorny Dzmitry , Kotelnikov Sergei , Chen Christopher S. , Hu Pingzhao , Denis Gerald V. , Kozakov Dima , Raught Brian , Siggers Trevor , Wuchty Stefan , Muthuswamy Senthil K. , Emili Andrew
Published: February 2023

A proper understanding of disease etiology will require longitudinal systems-scale reconstruction of the multitiered architecture of eukaryotic signaling. Here we combine state-of-the-art data acquisition platforms and bioinformatics tools to devise PAMAF, a workflow that simultaneously examines twelve omics modalities, i.e., protein abundance from whole-cells, nucleus, exosomes, secretome and membrane; N-glycosylation, phosphorylation; metabolites; mRNA, miRNA; and, in parallel, single-cell transcriptomes. We apply PAMAF in an established in vitro model of TGFβ-induced epithelial to mesenchymal transition (EMT) to quantify >61,000 molecules from 12 omics and 10 timepoints over 12 days. Bioinformatics analysis of this EMT-ExMap resource allowed us to identify; –topological coupling between omics, –four distinct cell states during EMT, –omics-specific kinetic paths, –stage-specific multi-omics characteristics, –distinct regulatory classes of genes, –ligand–receptor mediated intercellular crosstalk by integrating scRNAseq and subcellular proteomics, and –combinatorial drug targets (e.g., Hedgehog signaling and CAMK-II) to inhibit EMT, which we validate using a 3D mammary duct-on-a-chip platform. Overall, this study provides a resource on TGFβ signaling and EMT.
Macroevolutionary diversity of traits and genomes in the model yeast genus Saccharomyces
Authors: Peris David , Ubbelohde Emily J. , Kuang Meihua Christina , Kominek Jacek , Langdon Quinn K. , Adams Marie , Koshalek Justin A. , Hulfachor Amanda Beth , Opulente Dana A. , Hall David J. , Hyma Katie , Fay Justin C. , Leducq Jean-Baptiste , Charron Guillaume , Landry Christian R. , Libkind Diego , Gonçalves Carla , Gonçalves Paula , Sampaio José Paulo , Wang Qi-Ming , Bai Feng-Yan , Wrobel Russel L. , Hittinger Chris Todd
Published: February 2023

Species is the fundamental unit to quantify biodiversity. In recent years, the model yeast Saccharomyces cerevisiae has seen an increased number of studies related to its geographical distribution, population structure, and phenotypic diversity. However, seven additional species from the same genus have been less thoroughly studied, which has limited our understanding of the macroevolutionary events leading to the diversification of this genus over the last 20 million years. Here, we show the geographies, hosts, substrates, and phylogenetic relationships for approximately 1,800 Saccharomyces strains, covering the complete genus with unprecedented breadth and depth. We generated and analyzed complete genome sequences of 163 strains and phenotyped 128 phylogenetically diverse strains. This dataset provides insights about genetic and phenotypic diversity within and between species and populations, quantifies reticulation and incomplete lineage sorting, and demonstrates how gene flow and selection have affected traits, such as galactose metabolism. These findings elevate the genus Saccharomyces as a model to understand biodiversity and evolution in microbial eukaryotes.
Mode locking of hole spin coherences in CsPb(Cl, Br)3 perovskite nanocrystals
Authors: Kirstein E. , Kopteva N. E. , Yakovlev D. R. , Zhukov E. A. , Kolobkova E. V. , Kuznetsova M. S. , Belykh V. V. , Yugova I. A. , Glazov M. M. , Bayer M. , Greilich A.
Published: February 2023

The spin physics of perovskite nanocrystals with confined electrons or holes is attracting increasing attention, both for fundamental studies and spintronic applications. Here, stable $${{{{{{{\rm{CsPb}}}}}}}}{({{{{{{{{\rm{Cl}}}}}}}}}_{0.56}{{{{{{{{\rm{Br}}}}}}}}}_{0.44})}_{3}$$
CsPb

(

Cl

0.56

Br

0.44

)

3

lead halide perovskite nanocrystals embedded in a fluorophosphate glass matrix are studied by time-resolved optical spectroscopy to unravel the coherent spin dynamics of holes and their interaction with nuclear spins of the 207Pb isotope. We demonstrate the spin mode locking effect provided by the synchronization of the Larmor precession of single hole spins in each nanocrystal in the ensemble that are excited periodically by a laser in an external magnetic field. The mode locking is enhanced by nuclei-induced frequency focusing. An ensemble spin dephasing time $${T}_{2}^{ * }$$

T

2

*

of a nanosecond and a single hole spin coherence time of T2 = 13 ns are measured. The developed theoretical model accounting for the mode locking and nuclear focusing for randomly oriented nanocrystals with perovskite band structure describes the experimental data very well.
Systematically attenuating DNA targeting enables CRISPR-driven editing in bacteria
Authors: Collias Daphne , Vialetto Elena , Yu Jiaqi , Co Khoa , Almási Éva d. H. , Rüttiger Ann-Sophie , Achmedov Tatjana , Strowig Till , Beisel Chase L.
Published: February 2023

Bacterial genome editing commonly relies on chromosomal cleavage with Cas nucleases to counter-select against unedited cells. However, editing normally requires efficient recombination and high transformation efficiencies, which are unavailable in most strains. Here, we show that systematically attenuating DNA targeting activity enables RecA-mediated repair in different bacteria, allowing chromosomal cleavage to drive genome editing. Attenuation can be achieved by altering the format or expression strength of guide (g)RNAs; using nucleases with reduced cleavage activity; or engineering attenuated gRNAs (atgRNAs) with disruptive hairpins, perturbed nuclease-binding scaffolds, non-canonical PAMs, or guide mismatches. These modifications greatly increase cell counts and even improve the efficiency of different types of edits for Cas9 and Cas12a in Escherichia coli and Klebsiella oxytoca. We further apply atgRNAs to restore ampicillin sensitivity in Klebsiella pneumoniae, establishing a resistance marker for genetic studies. Attenuating DNA targeting thus offers a counterintuitive means to achieve CRISPR-driven editing across bacteria.
Broadly neutralizing SARS-CoV-2 antibodies through epitope-based selection from convalescent patients
Authors: Rouet Romain , Henry Jake Y. , Johansen Matt D. , Sobti Meghna , Balachandran Harikrishnan , Langley David B. , Walker Gregory J. , Lenthall Helen , Jackson Jennifer , Ubiparipovic Stephanie , Mazigi Ohan , Schofield Peter , Burnett Deborah L. , Brown Simon H. J. , Martinello Marianne , Hudson Bernard , Gilroy Nicole , Post Jeffrey J. , Kelleher Anthony , Jäck Hans-Martin , Goodnow Christopher C. , Turville Stuart G. , Rawlinson William D. , Bull Rowena A. , Stewart Alastair G. , Hansbro Philip M. , Christ Daniel
Published: February 2023

Emerging variants of concern (VOCs) are threatening to limit the effectiveness of SARS-CoV-2 monoclonal antibodies and vaccines currently used in clinical practice; broadly neutralizing antibodies and strategies for their identification are therefore urgently required. Here we demonstrate that broadly neutralizing antibodies can be isolated from peripheral blood mononuclear cells of convalescent patients using SARS-CoV-2 receptor binding domains carrying epitope-specific mutations. This is exemplified by two human antibodies, GAR05, binding to epitope class 1, and GAR12, binding to a new epitope class 6 (located between class 3 and 5). Both antibodies broadly neutralize VOCs, exceeding the potency of the clinical monoclonal sotrovimab (S309) by orders of magnitude. They also provide prophylactic and therapeutic in vivo protection of female hACE2 mice against viral challenge. Our results indicate that exposure to SARS-CoV-2 induces antibodies that maintain broad neutralization against emerging VOCs using two unique strategies: either by targeting the divergent class 1 epitope in a manner resistant to VOCs (ACE2 mimicry, as illustrated by GAR05 and mAbs P2C-1F11/S2K14); or alternatively, by targeting rare and highly conserved epitopes, such as the new class 6 epitope identified here (as illustrated by GAR12). Our results provide guidance for next generation monoclonal antibody development and vaccine design.
Temporal-iCLIP captures co-transcriptional RNA-protein interactions
Authors: Cordiner Ross A. , Dou Yuhui , Thomsen Rune , Bugai Andrii , Granneman Sander , Heick Jensen Torben
Published: February 2023

Dynamic RNA-protein interactions govern the co-transcriptional packaging of RNA polymerase II (RNAPII)-derived transcripts. Yet, our current understanding of this process in vivo primarily stems from steady state analysis. To remedy this, we here conduct temporal-iCLIP (tiCLIP), combining RNAPII transcriptional synchronisation with UV cross-linking of RNA-protein complexes at serial timepoints. We apply tiCLIP to the RNA export adaptor, ALYREF; a component of the Nuclear Exosome Targeting (NEXT) complex, RBM7; and the nuclear cap binding complex (CBC). Regardless of function, all tested factors interact with nascent RNA as it exits RNAPII. Moreover, we demonstrate that the two transesterification steps of pre-mRNA splicing temporally separate ALYREF and RBM7 binding to splicing intermediates, and that exon-exon junction density drives RNA 5′end binding of ALYREF. Finally, we identify underappreciated steps in snoRNA 3′end processing performed by RBM7. Altogether, our data provide a temporal view of RNA-protein interactions during the early phases of transcription.
Cartography of Genomic Interactions Enables Deep Analysis of Single-Cell Expression Data
Authors: Islam Md Tauhidul , Xing Lei
Published: February 2023

Remarkable advances in single cell genomics have presented unique challenges and opportunities for interrogating a wealth of biomedical inquiries. High dimensional genomic data are inherently complex because of intertwined relationships among the genes. Existing methods, including emerging deep learning-based approaches, do not consider the underlying biological characteristics during data processing, which greatly compromises the performance of data analysis and hinders the maximal utilization of state-of-the-art genomic techniques. In this work, we develop an entropy-based cartography strategy to contrive the high dimensional gene expression data into a configured image format, referred to as genomap, with explicit integration of the genomic interactions. This unique cartography casts the gene-gene interactions into the spatial configuration of genomaps and enables us to extract the deep genomic interaction features and discover underlying discriminative patterns of the data. We show that, for a wide variety of applications (cell clustering and recognition, gene signature extraction, single cell data integration, cellular trajectory analysis, dimensionality reduction, and visualization), the proposed approach drastically improves the accuracies of data analyses as compared to the state-of-the-art techniques.
Discovery and optimization of a broadly-neutralizing human monoclonal antibody against long-chain α-neurotoxins from snakes
Authors: Ledsgaard Line , Wade Jack , Jenkins Timothy P. , Boddum Kim , Oganesyan Irina , Harrison Julian A. , Villar Pedro , Leah Rachael A. , Zenobi Renato , Schoffelen Sanne , Voldborg Bjørn , Ljungars Anne , McCafferty John , Lomonte Bruno , Gutiérrez José M. , Laustsen Andreas H. , Karatt-Vellatt Aneesh
Published: February 2023

Snakebite envenoming continues to claim many lives across the globe, necessitating the development of improved therapies. To this end, broadly-neutralizing human monoclonal antibodies may possess advantages over current plasma-derived antivenoms by offering superior safety and high neutralization capacity. Here, we report the establishment of a pipeline based on phage display technology for the discovery and optimization of high affinity broadly-neutralizing human monoclonal antibodies. This approach yielded a recombinant human antibody with superior broadly-neutralizing capacities in vitro and in vivo against different long-chain α-neurotoxins from elapid snakes. This antibody prevents lethality induced by Naja kaouthia whole venom at an unprecedented low molar ratio of one antibody per toxin and prolongs the survival of mice injected with Dendroaspis polylepis or Ophiophagus hannah whole venoms.
Aberrant phase separation and nucleolar dysfunction in rare genetic diseases
Authors: Mensah Martin A. , Niskanen Henri , Magalhaes Alexandre P. , Basu Shaon , Kircher Martin , Sczakiel Henrike L. , Reiter Alisa M. V. , Elsner Jonas , Meinecke Peter , Biskup Saskia , Chung Brian H. Y. , Dombrowsky Gregor , Eckmann-Scholz Christel , Hitz Marc Phillip , Hoischen Alexander , Holterhus Paul-Martin , Hülsemann Wiebke , Kahrizi Kimia , Kalscheuer Vera M. , Kan Anita , Krumbiegel Mandy , Kurth Ingo , Leubner Jonas , Longardt Ann Carolin , Moritz Jörg D. , Najmabadi Hossein , Skipalova Karolina , Snijders Blok Lot , Tzschach Andreas , Wiedersberg Eberhard , Zenker Martin , Garcia-Cabau Carla , Buschow René , Salvatella Xavier , Kraushar Matthew L. , Mundlos Stefan , Caliebe Almuth , Spielmann Malte , Horn Denise , Hnisz Denes
Published: February 2023

Thousands of genetic variants in protein-coding genes have been linked to disease. However, the functional impact of most variants is unknown as they occur within intrinsically disordered protein regions that have poorly defined functions1–3. Intrinsically disordered regions can mediate phase separation and the formation of biomolecular condensates, such as the nucleolus4,5. This suggests that mutations in disordered proteins may alter condensate properties and function6–8. Here we show that a subset of disease-associated variants in disordered regions alter phase separation, cause mispartitioning into the nucleolus and disrupt nucleolar function. We discover de novo frameshift variants in HMGB1 that cause brachyphalangy, polydactyly and tibial aplasia syndrome, a rare complex malformation syndrome. The frameshifts replace the intrinsically disordered acidic tail of HMGB1 with an arginine-rich basic tail. The mutant tail alters HMGB1 phase separation, enhances its partitioning into the nucleolus and causes nucleolar dysfunction. We built a catalogue of more than 200,000 variants in disordered carboxy-terminal tails and identified more than 600 frameshifts that create arginine-rich basic tails in transcription factors and other proteins. For 12 out of the 13 disease-associated variants tested, the mutation enhanced partitioning into the nucleolus, and several variants altered rRNA biogenesis. These data identify the cause of a rare complex syndrome and suggest that a large number of genetic variants may dysregulate nucleoli and other biomolecular condensates in humans.
Dissecting cell identity via network inference and in silico gene perturbation
Authors: Kamimoto Kenji , Stringa Blerta , Hoffmann Christy M. , Jindal Kunal , Solnica-Krezel Lilianna , Morris Samantha A.
Published: February 2023

Cell identity is governed by the complex regulation of gene expression, represented as gene-regulatory networks1. Here we use gene-regulatory networks inferred from single-cell multi-omics data to perform in silico transcription factor perturbations, simulating the consequent changes in cell identity using only unperturbed wild-type data. We apply this machine-learning-based approach, CellOracle, to well-established paradigms—mouse and human haematopoiesis, and zebrafish embryogenesis—and we correctly model reported changes in phenotype that occur as a result of transcription factor perturbation. Through systematic in silico transcription factor perturbation in the developing zebrafish, we simulate and experimentally validate a previously unreported phenotype that results from the loss of noto, an established notochord regulator. Furthermore, we identify an axial mesoderm regulator, lhx1a. Together, these results show that CellOracle can be used to analyse the regulation of cell identity by transcription factors, and can provide mechanistic insights into development and differentiation.
The cellular coding of temperature in the mammalian cortex
Authors: Vestergaard M. , Carta M. , Güney G. , Poulet J. F. A.
Published: February 2023

Temperature is a fundamental sensory modality separate from touch, with dedicated receptor channels and primary afferent neurons for cool and warm1–3. Unlike for other modalities, however, the cortical encoding of temperature remains unknown, with very few cortical neurons reported that respond to non-painful temperature, and the presence of a ‘thermal cortex’ is debated4–8. Here, using widefield and two-photon calcium imaging in the mouse forepaw system, we identify cortical neurons that respond to cooling and/or warming with distinct spatial and temporal response properties. We observed a representation of cool, but not warm, in the primary somatosensory cortex, but cool and warm in the posterior insular cortex (pIC). The representation of thermal information in pIC is robust and somatotopically arranged, and reversible manipulations show a profound impact on thermal perception. Despite being positioned along the same one-dimensional sensory axis, the encoding of cool and that of warm are distinct, both in highly and broadly tuned neurons. Together, our results show that pIC contains the primary cortical representation of skin temperature and may help explain how the thermal system generates sensations of cool and warm.
High-throughput computation of Raman spectra from first principles
Authors: Bagheri Mohammad , Komsa Hannu-Pekka
Published: February 2023

Raman spectroscopy is a widely-used non-destructive material characterization method, which provides information about the vibrational modes of the material and therefore of its atomic structure and chemical composition. Interpretation of the spectra requires comparison to known references and to this end, experimental databases of spectra have been collected. Reference Raman spectra could also be simulated using atomistic first-principles methods but these are computationally demanding and thus the existing databases of computational Raman spectra are fairly small. In this work, we developed an optimized workflow to calculate the Raman spectra efficiently and taking full advantage of the phonon properties found in existing material databases. The workflow was benchmarked and validated by comparison to experiments and previous computational methods for select technologically relevant material systems. Using the workflow, we performed high-throughput calculations for a large set of materials (5099) belonging to many different material classes, and collected the results to a database. Finally, the contents of database are analyzed and the calculated spectra are shown to agree well with the experimental ones.
Gridded Datasets for Japan: Total, Male, and Female Populations from 2001–2020
Authors: Li Chao , Managi Shunsuke
Published: February 2023

Japan is a highly urbanized and severely aging society. In an aging society, chronic disease and disability are prevalent, and the population is sensitive to environmental issues and climate change. To identify the effects of population changes, formulate population and public health policies, and assist environmental projects, a high-resolution and accurate gridded population dataset is highly desirable. To provide basic data for research in these areas, we created an open access annual dataset from 2001 to 2020 containing the total, male, and female population counts in each grid at a resolution of 500 m. A random forest method was employed to fill the gaps in Japan’s nationwide census data collected in 2005, 2010, 2015, and 2020. The yearly population dataset was based on the 4th-level mesh data from the Statistics Bureau of Japan to make it easy to use. The dataset is provided here along with descriptions of the data and methods used in the fitting, cross-validation, and prediction processes.
Combating cholera by building predictive capabilities for pathogenic Vibrio cholerae in Yemen
Authors: Usmani Moiz , Brumfield Kyle D. , Magers Bailey M. , Chaves-Gonzalez Juan , Ticehurst Helen , Barciela Rosa , McBean Fergus , Colwell Rita R. , Jutla Antarpreet
Published: February 2023

Cholera remains a global public health threat in regions where social vulnerabilities intersect with climate and weather processes that impact infectious Vibrio cholerae. While access to safe drinking water and sanitation facilities limit cholera outbreaks, sheer cost of building such infrastructure limits the ability to safeguard the population. Here, using Yemen as an example where cholera outbreak was reported in 2016, we show how predictive abilities for forecasting risk, employing sociodemographical, microbiological, and climate information of cholera, can aid in combating disease outbreak. An epidemiological analysis using Bradford Hill Criteria was employed in near-real-time to understand a predictive model’s outputs and cholera cases in Yemen. We note that the model predicted cholera risk at least four weeks in advance for all governorates of Yemen with overall 72% accuracy (varies with the year). We argue the development of anticipatory decision-making frameworks for climate modulated diseases to design intervention activities and limit exposure of pathogens preemptively.
Piecewise-potential-field-based path planning method for fixed-wing UAV formation
Authors: Fang Yuxuan , Yao Yiping , Zhu Feng , Chen Kai
Published: February 2023

The multi-UAV path planning method based on artificial potential field (APF) has the advantage of rapid processing speed and the ability to deal with dynamic obstacles, though some problems remain—such as a lack of consideration of the initial heading constraint of the UAVs, making it easy to fall into a local minimum trap, and the path not being sufficiently smooth. Consequently, a fixed-wing UAV formation path planning method based on piecewise potential field (PPF) is proposed, where the problem of UAV formation flight path planning in different states can be solved by suitable design of the PPF function. Firstly, the potential field vector can be used to represent the potential field functions of obstacles and target points to meet the kinematic constraints of the UAV. Secondly, the local minimum region can be detected, the additional potential field vector being set to break away from this region. Finally, the change rules of the potential field vector of a UAV in the formation reconstruction scene can be designed, a smooth formation flight track being assured by adjusting the corresponding speed of each UAV track point. Considering the path planning of a five-UAV formation as an example, we conducted simulation experiments. The results showed that—compared with the existing methods based on APF—the results obtained using the PPF-based method considered the initial heading limits of the UAVs, the planned path being considerably smoother. Moreover, the proposed method could plan multiple UAV tracks, satisfying the known constraints without conflict in complex scenarios.
Ecological successions throughout the desiccation of Tirez lagoon (Spain) as an astrobiological time-analog for wet-to-dry transitions on Mars
Authors: Fairén Alberto G. , Rodríguez Nuria , Sánchez-García Laura , Rojas Patricia , Uceda Esther R. , Carrizo Daniel , Amils Ricardo , Sanz José L.
Published: February 2023

Tirez was a small and seasonal endorheic athalassohaline lagoon that was located in central Spain. In recent years, the lagoon has totally dried out, offering for the first time the opportunity to analyze its desiccation process as a “time-analog” to similar events occurred in paleolakes with varying salinity during the wet-to-dry transition on early Mars. On the martian cratered highlands, an early period of water ponding within enclosed basins evolved to a complete desiccation of the lakes, leading to deposition of evaporitic sequences during the Noachian and into the Late Hesperian. As Tirez also underwent a process of desiccation, here we describe (i) the microbial ecology of Tirez when the lagoon was still active 20 years ago, with prokaryotes adapted to extreme saline conditions; (ii) the composition of the microbial community in the dried lake sediments today, in many case groups that thrive in sediments of extreme environments; and (iii) the molecular and isotopic analysis of the lipid biomarkers that can be recovered from the sediments today. We discuss the implications of these results to better understanding the ecology of possible Martian microbial communities during the wet-to-dry transition at the end of the Hesperian, and how they may inform about research strategies to search for possible biomarkers in Mars after all the water was lost.
Pleural fluid microbiota as a biomarker for malignancy and prognosis
Authors: Kwok Benjamin , Wu Benjamin G. , Kocak Ibrahim F. , Sulaiman Imran , Schluger Rosemary , Li Yonghua , Anwer Raheel , Goparaju Chandra , Ryan Daniel J. , Sagatelian Marla , Dreier Matthew S. , Murthy Vivek , Rafeq Samaan , Michaud Gaetane C. , Sterman Daniel H. , Bessich Jamie L. , Pass Harvey I. , Segal Leopoldo N. , Tsay Jun-Chieh J.
Published: February 2023

Malignant pleural effusions (MPE) complicate malignancies and portend worse outcomes. MPE is comprised of various components, including immune cells, cancer cells, and cell-free DNA/RNA. There have been investigations into using these components to diagnose and prognosticate MPE. We hypothesize that the microbiome of MPE is unique and may be associated with diagnosis and prognosis. We compared the microbiota of MPE against microbiota of pleural effusions from non-malignant and paramalignant states. We collected a total of 165 pleural fluid samples from 165 subjects; Benign (n = 16), Paramalignant (n = 21), MPE-Lung (n = 57), MPE-Other (n = 22), and Mesothelioma (n = 49). We performed high throughput 16S rRNA gene sequencing on pleural fluid samples and controls. We showed that there are compositional differences among pleural effusions related to non-malignant, paramalignant, and malignant disease. Furthermore, we showed differential enrichment of bacterial taxa within MPE depending on the site of primary malignancy. Pleural fluid of MPE-Lung and Mesothelioma were associated with enrichment with oral and gut bacteria that are commonly thought to be commensals, including Rickettsiella, Ruminococcus, Enterococcus, and Lactobacillales. Mortality in MPE-Lung is associated with enrichment in Methylobacterium, Blattabacterium, and Deinococcus. These observations lay the groundwork for future studies that explore host-microbiome interactions and their influence on carcinogenesis.
Prevalence and influencing factors of wheeze and asthma among preschool children in Urumqi city: a cross-sectional survey
Authors: Wang Tingting , Shi Haonan , Wan Guangsheng , Zhao Zhuohui , Norback Dan , Pu Guiping , Ma Shaowei , Dong Huijuan , Yao Jian , Lu Junwen , Wang Yue , Yan Qi , Qi Huizhen , Ma Qi , Shi Yufeng
Published: February 2023

To investigate the prevalence and indoor environmental influencing factors of wheeze and asthma among preschool children in Urumqi, Xinjiang, China to provide a strong basis for prevention and control. In August 2019, a cross-sectional study involving 8153 preschool children was conducted in 60 kindergartens in Urumqi. The ALLHOME-2 questionnaire was used for childhood wheeze and asthma survey, and the dampness in buildings and health (DBH) questionnaire was used for the childhood home dwelling and living environment survey. Multivariate unconditional logistic regression was then used to analyze the potential influencing factors of childhood asthma and wheeze. The prevalence of wheeze and asthma in children was 4.7% and 2.0%, respectively. Multivariate unconditional logistic regression results suggested that ethnicity other than the Han Chinese (odds ratio (OR) 1.39, 95% confidence interval (CI) 1.05–1.84), caesarean section (OR 1.24, 95% CI 1.00–1.53), family history of asthma (OR 5.00, 95% CI 3.36–7.44), carpet or floor bedding at home (OR 1.40, 95% CI 1.05–1.87), purchasing new furniture in the mother’s residence during pregnancy (OR 1.58, 95% CI 1.06–2.36), pet keeping in the residence at aged 0–1 year (OR 1.55, 95% CI 1.13–2.13), passive smoking by child in the current residence (OR 1.35, 95% CI 1.01–1.80), and having mould or hygroma in the child's residence at aged 0–1 year (OR 1.72, 95% CI 1.12–2.64) were risk factors for wheeze. In addition, Girls (OR 0.73, 95% CI 0.59–0.90) was a protective factor for wheeze. Caesarean section (OR 1.46, 95% CI 1.06–2.00), family history of asthma (OR 7.06, 95% CI 4.33–11.53), carpet or floor bedding at home (OR 2.20, 95% CI 1.50–3.23), and pet keeping in the residence at aged 0–1 year (OR 1.64, 95% CI 1.04–1.83) were risk factors for asthma, whereas Girls (OR 0.58, 95% CI 0.42–0.80) was a protective factor for asthma. This survey indicates that the purchase of new furniture, the placement of carpet or floor bedding in the child's residence, the pets keeping, room dampness or moldy phenomena, and passive smoking may all contribute to an elevated risk of wheeze or asthma in children.