bluuebunny/crossref_metadata_2025_split huggingface dataset:
Secondary Formation of Submicron and Supermicron Organic and Inorganic Aerosols in a Highly Polluted Urban Area
Authors: Zheng Yan , Miao Ruqian , Zhang Qi , Li Yaowei , Cheng Xi , Liao Keren , Koenig Theodore K. , Ge Yanli , Tang Lizi , Shang Dongjie , Hu Min , Chen Shiyi , Chen Qi 
Published: February 2023

AbstractDifferent adverse health effects of submicron (PM1) and fine particles (PM2.5) may be attributed to their chemical differences, requiring a better understanding of size‐resolved composition. Herein, extensive online measurements were conducted across seasons in Beijing by two aerosol mass spectrometers, one of which alternately sampled PM1 and PM2.5. Source apportionment of organic aerosol (OA) indicated that traffic‐ and cooking‐related OA together accounted for ∼20%−30% of the OA mass in PM2.5, showing insignificant seasonal variations. Coal‐combustion and biomass‐burning‐related OA had minor contributions. The two secondary OA (SOA) factors together accounted for 59%−73% of the OA mass in PM2.5. The mass distributions of particulate components in PM1 and PM2.5 varied greatly across seasons. Secondary formation played a key role in particle size growth during cold seasons. During severe hazes with high aerosol liquid water content (ALWC), the supermicron mass fraction (MF1−2.5) of secondary components reached ∼40%−50% while those for primary OA remained at ∼20%. Heterogeneous uptake, aqueous processing, and dissolution likely all contributed to the enhanced concentration of secondary components, and the former two were perhaps more important. The increase of MF1−2.5 for secondary components with increasing ALWC in spring was less than that in winter, possibly due to the shorter duration of stagnant conditions limiting secondary formation. Early autumn showed higher MF1−2.5 values than cold seasons with insignificant changes as ALWC varied, plausibly explained by intensive new particle formation hindering persistent particle growth. Our results highlight the importance of heterogeneous uptake and aqueous processing in distributing SOA in supermicron mode in polluted areas.
Automatic Ionospheric Weather Monitoring With DPS‐4D Ionosonde and ARTIST‐5 Autoscaler: System Performance at a Mid‐Latitude Observatory
Authors: Stankov S. M. , Verhulst T. G. W. , Sapundjiev D. 
Published: February 2023

AbstractThe performance of the digital ionospheric sounder at the mid‐latitude site of Dourbes, Belgium (4.6°E, 50.1°N) is evaluated and detailed here in terms of its capability to deliver ionograms of good quality at different sounding rates together with the quality of the automated scaling of ionospheric characteristics done by the dedicated computer software. The instrument is a Lowell Digisonde‐4D, also known as the Digital Portable Sounder 4D (DPS‐4D), equipped with the latest version 5 of the autoscaling software, Automatic Real‐Time Ionogram Scaler with True height. A thorough statistical analysis has been carried out of the automatic processing and scaling of the key ionospheric characteristics: critical frequencies, virtual heights, maximum usable frequency, and propagation factor. This analysis is based on the manually scaled hourly values of the above‐mentioned characteristics for the time period since the installation of the DPS‐4D in April 2011. Based on the analysis, the error bounds (with 95% probability) have been determined for each characteristic. Results are expected to be of particular interest to researchers, developers and users of the great variety of ionosphere/space weather monitoring services worldwide.
Defining the heterogeneity of unbalanced structural variation underlying breast cancer susceptibility by nanopore genome sequencing
Authors: Dixon Katherine , Shen Yaoqing , O’Neill Kieran , Mungall Karen L. , Chan Simon , Bilobram Steve , Zhang Wei , Bezeau Marjorie , Sharma Alshanee , Fok Alexandra , Mungall Andrew J. , Moore Richard , Bosdet Ian , Thibodeau My Linh , Sun Sophie , Yip Stephen , Schrader Kasmintan A. , Jones Steven J. M. 
Published: February 2023

AbstractGermline structural variants (SVs) are challenging to resolve by conventional genetic testing assays. Long-read sequencing has improved the global characterization of SVs, but its sensitivity at cancer susceptibility loci has not been reported. Nanopore long-read genome sequencing was performed for nineteen individuals with pathogenic copy number alterations in BRCA1, BRCA2, CHEK2 and PALB2 identified by prior clinical testing. Fourteen variants, which spanned single exons to whole genes and included a tandem duplication, were accurately represented. Defining the precise breakpoints of SVs in BRCA1 and CHEK2 revealed unforeseen allelic heterogeneity and informed the mechanisms underlying the formation of recurrent deletions. Integrating read-based and statistical phasing further helped define extended haplotypes associated with founder alleles. Long-read sequencing is a sensitive method for characterizing private, recurrent and founder SVs underlying breast cancer susceptibility. Our findings demonstrate the potential for nanopore sequencing as a powerful genetic testing assay in the hereditary cancer setting.
Tandemly duplicated CYP82Ds catalyze 14-hydroxylation in triptolide biosynthesis and precursor production in Saccharomyces cerevisiae
Authors: Zhang Yifeng , Gao Jie , Ma Lin , Tu Lichan , Hu Tianyuan , Wu Xiaoyi , Su Ping , Zhao Yujun , Liu Yuan , Li Dan , Zhou Jiawei , Yin Yan , Tong Yuru , Zhao Huan , Lu Yun , Wang Jiadian , Gao Wei , Huang Luqi 
Published: February 2023

AbstractTriptolide is a valuable multipotent antitumor diterpenoid in Tripterygium wilfordii, and its C-14 hydroxyl group is often selected for modification to enhance both the bioavailability and antitumor efficacy. However, the mechanism for 14-hydroxylation formation remains unknown. Here, we discover 133 kb of tandem duplicated CYP82Ds encoding 11 genes on chromosome 12 and characterize CYP82D274 and CYP82D263 as 14-hydroxylases that catalyze the metabolic grid in triptolide biosynthesis. The two CYP82Ds catalyze the aromatization of miltiradiene, which has been repeatedly reported to be a spontaneous process. In vivo assays and evaluations of the kinetic parameters of CYP82Ds indicate the most significant affinity to dehydroabietic acid among multiple intermediates. The precursor 14-hydroxy-dehydroabietic acid is successfully produced by engineered Saccharomyces cerevisiae. Our study provides genetic elements for further elucidation of the downstream biosynthetic pathways and heterologous production of triptolide and of the currently intractable biosynthesis of other 14-hydroxyl labdane-type secondary metabolites.
From nanohole to ultralong straight nanochannel fabrication in graphene oxide with swift heavy ions
Authors: Olejniczak Andrzej , Rymzhanov Ruslan A. 
Published: February 2023

AbstractPorous architectures based on graphene oxide with precisely tailored nm-sized pores are attractive for biofluidic applications such as molecular sieving, DNA sequencing, and recognition-based sensing. However, the existing pore fabrication methods are complex, suffer from insufficient control over the pore density and uniformity, or are not scalable to large areas. Notably, creating vertical pores in multilayer films appears to be particularly difficult. Here, we show that uniform 6–7 nm-sized holes and straight, vertical nanochannels can be formed by simply irradiating graphene oxide (GO) films with high-energy heavy ions. Long penetration depths of energetic ions in combination with localized energy deposition and effective self-etching processes enable the creation of through pores even in 10 µm-thick GO films. This fully scalable fabrication provides a promising possibility for obtaining innovative GO track membranes.
Structural basis for membrane attack complex inhibition by CD59
Authors: Couves Emma C. , Gardner Scott , Voisin Tomas B. , Bickel Jasmine K. , Stansfeld Phillip J. , Tate Edward W. , Bubeck Doryen 
Published: February 2023

AbstractCD59 is an abundant immuno-regulatory receptor that protects human cells from damage during complement activation. Here we show how the receptor binds complement proteins C8 and C9 at the membrane to prevent insertion and polymerization of membrane attack complex (MAC) pores. We present cryo-electron microscopy structures of two inhibited MAC precursors known as C5b8 and C5b9. We discover that in both complexes, CD59 binds the pore-forming β-hairpins of C8 to form an intermolecular β-sheet that prevents membrane perforation. While bound to C8, CD59 deflects the cascading C9 β-hairpins, rerouting their trajectory into the membrane. Preventing insertion of C9 restricts structural transitions of subsequent monomers and indirectly halts MAC polymerization. We combine our structural data with cellular assays and molecular dynamics simulations to explain how the membrane environment impacts the dual roles of CD59 in controlling pore formation of MAC, and as a target of bacterial virulence factors which hijack CD59 to lyse human cells.
Dual-comb optical activity spectroscopy for the analysis of vibrational optical activity induced by external magnetic field
Authors: Peng Daowang , Gu Chenglin , Zuo Zhong , Di Yuanfeng , Zou Xing , Tang Lulu , Deng Lunhua , Luo Daping , Liu Yang , Li Wenxue 
Published: February 2023

AbstractOptical activity (OA) spectroscopy is a powerful tool to characterize molecular chirality, explore the stereo-specific structure and study the solution-state conformation of biomolecules, which is widely utilized in the fields of molecular chirality, pharmaceutics and analytical chemistry. Due to the considerably weak effect, OA spectral analysis has high demands on measurement speed and sensitivity, especially for organic biomolecules. Moreover, gas-phase OA measurements require higher resolution to resolve Doppler-limited profiles. Here, we show the unmatched potential of dual-comb spectroscopy (DCS) in magnetic optical activity spectroscopy (MOAS) of gas-phase molecules with the resolution of hundred-MHz level and the high-speed measurement of sub-millisecond level. As a demonstration, we achieved the rapid, high-precision and high-resolution MOAS measurement of the nitrogen dioxide $${\upsilon }_{1}$$

υ

1

+$${\upsilon }_{3}$$

υ

3

band and the nitric oxide overtone band, which can be used to analyze fine structure of molecules. Besides, the preliminary demonstration of liquid-phase chiroptical activity (as weak as 10−5) has been achieved with several seconds of sampling time, which could become a routine approach enabling ultrafast dynamics analysis of chiral structural conformations.
Spatial proteomics reveals secretory pathway disturbances caused by neuropathy-associated TECPR2
Authors: Nalbach Karsten , Schifferer Martina , Bhattacharya Debjani , Ho-Xuan Hung , Tseng Wei Chou , Williams Luis A. , Stolz Alexandra , Lichtenthaler Stefan F. , Elazar Zvulun , Behrends Christian 
Published: February 2023

AbstractHereditary sensory and autonomic neuropathy 9 (HSAN9) is a rare fatal neurological disease caused by mis- and nonsense mutations in the gene encoding for Tectonin β-propeller repeat containing protein 2 (TECPR2). While TECPR2 is required for lysosomal consumption of autophagosomes and ER-to-Golgi transport, it remains elusive how exactly TECPR2 is involved in autophagy and secretion and what downstream sequels arise from defective TECPR2 due to its involvement in these processes. To address these questions, we determine molecular consequences of TECPR2 deficiency along the secretory pathway. By employing spatial proteomics, we describe pronounced changes with numerous proteins important for neuronal function being affected in their intracellular transport. Moreover, we provide evidence that TECPR2’s interaction with the early secretory pathway is not restricted to COPII carriers. Collectively, our systematic profiling of a HSAN9 cell model points to specific trafficking and sorting defects which might precede autophagy dysfunction upon TECPR2 deficiency.
Deconstructing the modular organization and real-time dynamics of mammalian spinal locomotor networks
Authors: Hsu Li-Ju , Bertho Maëlle , Kiehn Ole 
Published: February 2023

AbstractLocomotion empowers animals to move. Locomotor-initiating signals from the brain are funneled through descending neurons in the brainstem that act directly on spinal locomotor circuits. Little is known in mammals about which spinal circuits are targeted by the command and how this command is transformed into rhythmicity in the cord. Here we address these questions leveraging a mouse brainstem-spinal cord preparation from either sex that allows locating the locomotor command neurons with simultaneous Ca2+ imaging of spinal neurons. We show that a restricted brainstem area – encompassing the lateral paragigantocellular nucleus (LPGi) and caudal ventrolateral reticular nucleus (CVL) – contains glutamatergic neurons which directly initiate locomotion. Ca2+ imaging captures the direct LPGi/CVL locomotor initiating command in the spinal cord and visualizes spinal glutamatergic modules that execute the descending command and its transformation into rhythmic locomotor activity. Inhibitory spinal networks are recruited in a distinctly different pattern. Our study uncovers the principal logic of how spinal circuits implement the locomotor command using a distinct modular organization.
Optimal age targeting for pneumococcal vaccination in older adults; a modelling study
Authors: Thindwa Deus , Clifford Samuel , Kleynhans Jackie , von Gottberg Anne , Walaza Sibongile , Meiring Susan , Swarthout Todd D. , Miller Elizabeth , McIntyre Peter , Andrews Nick , Amin-Chowdhury Zahin , Fry Norman , Jambo Kondwani C. , French Neil , Almeida Samanta Cristine Grassi , Ladhani Shamez N. , Heyderman Robert S. , Cohen Cheryl , de Cunto Brandileone Maria Cristina , Flasche Stefan 
Published: February 2023

AbstractInvasive pneumococcal disease (IPD) risk increases with age for older adults whereas the population size benefiting from pneumococcal vaccines and robustness of immunogenic response to vaccination decline. We estimate how demographics, vaccine efficacy/effectiveness (VE), and waning VE impact on optimal age for a single-dose pneumococcal vaccination. Age- and vaccine-serotype-specific IPD cases from routine surveillance of adults ≥ 55 years old (y), ≥ 4-years after infant-pneumococcal vaccine introduction and before 2020, and VE data from prior studies were used to estimate IPD incidence and waning VE which were then combined in a cohort model of vaccine impact. In Brazil, Malawi, South Africa and England 51, 51, 54 and 39% of adults older than 55 y were younger than 65 years old, with a smaller share of annual IPD cases reported among < 65 years old in England (4,657; 20%) than Brazil (186; 45%), Malawi (4; 63%), or South Africa (134, 48%). Vaccination at 55 years in Brazil, Malawi, and South Africa, and at 70 years in England had the greatest potential for IPD prevention. Here, we show that in low/middle-income countries, pneumococcal vaccines may prevent a substantial proportion of residual IPD burden if administered earlier in adulthood than is typical in high-income countries.
A trans-kingdom T6SS effector induces the fragmentation of the mitochondrial network and activates innate immune receptor NLRX1 to promote infection
Authors: Sá-Pessoa Joana , López-Montesino Sara , Przybyszewska Kornelia , Rodríguez-Escudero Isabel , Marshall Helina , Ova Adelia , Schroeder Gunnar N. , Barabas Peter , Molina María , Curtis Tim , Cid Víctor J. , Bengoechea José A. 
Published: February 2023

AbstractBacteria can inhibit the growth of other bacteria by injecting effectors using a type VI secretion system (T6SS). T6SS effectors can also be injected into eukaryotic cells to facilitate bacterial survival, often by targeting the cytoskeleton. Here, we show that the trans-kingdom antimicrobial T6SS effector VgrG4 from Klebsiella pneumoniae triggers the fragmentation of the mitochondrial network. VgrG4 colocalizes with the endoplasmic reticulum (ER) protein mitofusin 2. VgrG4 induces the transfer of Ca2+ from the ER to the mitochondria, activating Drp1 (a regulator of mitochondrial fission) thus leading to mitochondrial network fragmentation. Ca2+ elevation also induces the activation of the innate immunity receptor NLRX1 to produce reactive oxygen species (ROS). NLRX1-induced ROS limits NF-κB activation by modulating the degradation of the NF-κB inhibitor IκBα. The degradation of IκBα is triggered by the ubiquitin ligase SCFβ-TrCP, which requires the modification of the cullin-1 subunit by NEDD8. VgrG4 abrogates the NEDDylation of cullin-1 by inactivation of Ubc12, the NEDD8-conjugating enzyme. Our work provides an example of T6SS manipulation of eukaryotic cells via alteration of the mitochondria.
Two-year clinical progression in focal and diffuse subtypes of Parkinson’s disease
Authors: Johansson Martin E. , van Lier Nina M. , Kessels Roy P. C. , Bloem Bastiaan R. , Helmich Rick C. 
Published: February 2023

AbstractHeterogeneity in Parkinson’s disease (PD) presents a barrier to understanding disease mechanisms and developing new treatments. This challenge may be partially overcome by stratifying patients into clinically meaningful subtypes. A recent subtyping scheme classifies de novo PD patients into three subtypes: mild-motor predominant, intermediate, or diffuse-malignant, based on motor impairment, cognitive function, rapid eye movement sleep behavior disorder (RBD) symptoms, and autonomic symptoms. We aimed to validate this approach in a large longitudinal cohort of early-to-moderate PD (n = 499) by assessing the influence of subtyping on clinical characteristics at baseline and on two-year progression. Compared to mild-motor predominant patients (42%), diffuse-malignant patients (12%) showed involvement of more clinical domains, more diffuse hypokinetic-rigid motor symptoms (decreased lateralization and hand/foot focality), and faster two-year progression. These findings extend the classification of diffuse-malignant and mild-motor predominant subtypes to early-to-moderate PD and suggest that different pathophysiological mechanisms (focal versus diffuse cerebral propagation) may underlie distinct subtype classifications.
Ionized carbon as a tracer of the assembly of interstellar clouds
Authors: Schneider Nicola , Bonne Lars , Bontemps Sylvain , Kabanovic Slawa , Simon Robert , Ossenkopf-Okada Volker , Buchbender Christof , Stutzki Jürgen , Mertens Marc , Ricken Oliver , Csengeri Timea , Tielens Alexander G.G.M. 
Published: February 2023

AbstractMolecular hydrogen clouds are a key component of the interstellar medium because they are the birthplaces for stars. They are embedded in atomic gas that pervades the interstellar space. However, the details of how molecular clouds assemble from and interact with the atomic gas are still largely unknown. As a result of new observations of the 158 μm line of ionized carbon [CII] in the Cygnus region within the FEEDBACK program on SOFIA (Stratospheric Observatory for Infrared Astronomy), we present compelling evidence that [CII] unveils dynamic interactions between cloud ensembles. This process is neither a head-on collision of fully molecular clouds nor a gentle merging of only atomic clouds. Moreover, we demonstrate that the dense molecular clouds associated with the DR21 and W75N star-forming regions and a cloud at higher velocity are embedded in atomic gas, and all components interact over a large range of velocities (roughly 20 km s−1). The atomic gas has a density of around 100 cm−3 and a temperature of roughly 100 K. We conclude that the [CII] 158 μm line is an excellent tracer to witness the processes involved in cloud interactions and anticipate further detections of this phenomenon in other regions.
TACCO unifies annotation transfer and decomposition of cell identities for single-cell and spatial omics
Authors: Mages Simon , Moriel Noa , Avraham-Davidi Inbal , Murray Evan , Watter Jan , Chen Fei , Rozenblatt-Rosen Orit , Klughammer Johanna , Regev Aviv , Nitzan Mor 
Published: February 2023

AbstractTransferring annotations of single-cell-, spatial- and multi-omics data is often challenging owing both to technical limitations, such as low spatial resolution or high dropout fraction, and to biological variations, such as continuous spectra of cell states. Based on the concept that these data are often best described as continuous mixtures of cells or molecules, we present a computational framework for the transfer of annotations to cells and their combinations (TACCO), which consists of an optimal transport model extended with different wrappers to annotate a wide variety of data. We apply TACCO to identify cell types and states, decipher spatiomolecular tissue structure at the cell and molecular level and resolve differentiation trajectories using synthetic and biological datasets. While matching or exceeding the accuracy of specialized tools for the individual tasks, TACCO reduces the computational requirements by up to an order of magnitude and scales to larger datasets (for example, considering the runtime of annotation transfer for 1 M simulated dropout observations).
Prediction of prime editing insertion efficiencies using sequence features and DNA repair determinants
Authors: Koeppel Jonas , Weller Juliane , Peets Elin Madli , Pallaseni Ananth , Kuzmin Ivan , Raudvere Uku , Peterson Hedi , Liberante Fabio Giuseppe , Parts Leopold 
Published: February 2023

AbstractMost short sequences can be precisely written into a selected genomic target using prime editing; however, it remains unclear what factors govern insertion. We design a library of 3,604 sequences of various lengths and measure the frequency of their insertion into four genomic sites in three human cell lines, using different prime editor systems in varying DNA repair contexts. We find that length, nucleotide composition and secondary structure of the insertion sequence all affect insertion rates. We also discover that the 3′ flap nucleases TREX1 and TREX2 suppress the insertion of longer sequences. Combining the sequence and repair features into a machine learning model, we can predict relative frequency of insertions into a site with R = 0.70. Finally, we demonstrate how our accurate prediction and user-friendly software help choose codon variants of common fusion tags that insert at high efficiency, and provide a catalog of empirically determined insertion rates for over a hundred useful sequences.