bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional hepatobiliary organoids recapitulate liver development and reveal essential drivers of hepatobiliary cell fate determination
Authors: He Juan , Cui Haoyue , Shi Xiaohan , Jin Qiqi , Han Ximeng , Han Tiantian , Peng Jiayin , Guo Shiwei , Zhang Lei , Zhao Yun , Zhou Bin , Chen Luonan , Chen Lei , Arial Zeng Yi , Wang Hongyang , Jin Gang , Gao Dong 
Published: December 2022

AbstractDuring liver development, hepatocytes, and cholangiocytes are concurrently differentiated from common liver progenitor cells and are assembled into hepatobiliary architecture to perform proper hepatic function. However, the generation of functional hepatobiliary architecture from hepatocytes in vitro is still challenging, and the exact molecular drivers of hepatobiliary cell lineage determination is largely unknown. In this study, functional hepatobiliary organoids (HBOs) are generated from hepatocytes. These HBOs contain a bile duct network surrounded by mature hepatocytes and stably maintain hepatic characteristics and function in vitro and upon transplantation in vivo. Morphological transition and expression profile of hepatocyte-derived organoids recapitulate the process of liver development. Gene regulation landscape of hepatocyte-derived organoids reveal that Tead4 and Ddit3 promote the cell fate commitment of liver progenitors to functional cholangiocytes and hepatocytes, respectively. Liver cell fate determination is reversed by inhibiting Tead4 or increasing Ddit3 expression both in vitro and upon transplantation in vivo. Collectively, hepatocyte-derived HBOs reveal the essential transcription drivers of liver hepatobiliary cell lineage determination and represent powerful models for liver development and regeneration.
Modelling the evolution of silicate/volatile accretion discs around white dwarfs
Authors: Okuya Ayaka , Ida Shigeru , Hyodo Ryuki , Okuzumi Satoshi 
Published: December 2022

ABSTRACT
A growing number of debris discs have been detected around metal-polluted white dwarfs. They are thought to be originated from tidally disrupted exoplanetary bodies and responsible for metal accretion on to host WDs. To explain (1) the observationally inferred accretion rate higher than that induced by Poynting–Robertson drag, $\dot{M}_{\rm PR}$, and (2) refractory-rich photosphere composition indicating the accretion of terrestrial rocky materials, previous studies proposed runaway accretion of silicate particles due to gas drag by the increasing silicate vapour produced by the sublimation of the particles. Because re-condensation of the vapour diffused beyond the sublimation line was neglected, we revisit this problem by one-dimensional advection/diffusion simulation that consistently incorporates silicate sublimation/condensation and back-reaction to particle drift due to gas drag in the solid-rich disc. We find that the silicate vapour density in the region overlapping the solid particles follows the saturating vapour pressure and that no runaway accretion occurs if the re-condensation is included. This always limits the accretion rate from mono-compositional silicate discs to $\dot{M}_{\rm PR}$ in the equilibrium state. Alternatively, by performing additional simulations that couple the volatile gas (e.g. water vapour), we demonstrate that the volatile gas enhances the silicate accretion to $\gt \dot{M}_{\rm PR}$ through gas drag. The refractory-rich accretion is simultaneously reproduced when the initial volatile fraction of disc is $\lesssim 10$ wt per cent because of the suppression of volatile accretion due to the efficient back-reaction of solid to gas. The discs originating from C-type asteroid analogues might be a possible clue to the high-$\dot{M}$ puzzle.
SPARCS-North Wide-field VLBI Survey: exploring the resolved μJy extragalactic radio source population with EVN + e-MERLIN
Authors: Njeri Ann , Beswick Robert J , Radcliffe Jack F , Thomson A P , Wrigley N , Muxlow T W B , Garrett M A , Deane Roger P , Moldon Javier , Norris Ray P , Kothes Roland 
Published: December 2022

ABSTRACT
The SKA PAthfinder Radio Continuum Surveys (SPARCS) are providing deep-field imaging of the faint (sub-mJy) extragalactic radio source populations through a series of reference surveys. One of the key science goals for SPARCS is to characterize the relative contribution of radio emission associated with active galactic nucleus (AGN) from star formation (SF) in these faint radio source populations, using a combination of high sensitivity and high angular resolution imaging over a range of spatial scales (arcsec to mas). To isolate AGN contribution from SF, we hypothesize that there exists a brightness temperature cut-off point separating pure AGN from SF. We present a multiresolution (10–100 mas) view of the transition between compact AGN and diffuse SF through a deep wide-field EVN + e-MERLIN, multiple phase centre survey of the centre of the Northern SPARCS (SLOAN) reference field at 1.6 GHz. This is the first (and only) VLBI (+ e-MERLIN) milliarcsecond angular resolution observation of this field, and of the wider SPARCS reference field programme. Using these high spatial resolution (9 pc–0.3 kpc at z ∼ 1.25) data, 11 milliarcsec-scale sources are detected from a targeted sample of 52 known radio sources from previous observations with the e-MERLIN, giving a VLBI detection fraction of $\sim 21{{\ \rm per\ cent}}$. At spatial scales of $\sim 9\,$pc, these sources show little to no jet structure whilst at $\sim 0.3\,$kpc one-sided and two-sided radio jets begin to emerge on the same sources, indicating a possible transition from pure AGN emissions to AGN and SF systems.
Ultraviolet imaging observations of three jellyfish galaxies: star formation suppression in the centre and ongoing star formation in stripped tails
Authors: George K , Poggianti B M , Tomičić N , Postma J , Côté P , Fritz J , Ghosh S K , Gullieuszik M , Hutchings J B , Moretti A , Omizzolo A , Radovich M , Sreekumar P , Subramaniam A , Tandon S N , Vulcani B 
Published: December 2022

ABSTRACT
Spiral galaxies undergo strong ram-pressure effects when they fall into the galaxy cluster potential. As a consequence, their gas is stripped to form extended tails within which star formation can happen, giving them the typical jellyfish appearance. The ultraviolet imaging observations of jellyfish galaxies provide an opportunity to understand ongoing star formation in the stripped tails. We report the ultraviolet observations of the jellyfish galaxies JW39, JO60, JO194 and compare with observations in optical continuum and Hα. We detect knots of star formation in the disc and tails of the galaxies and find that their UV and Hα flux are well correlated. The optical emission line ratio maps of these galaxies are used to identify for every region the emission mechanism, due to either star formation, LINER or a mix of the two phenomena. The star-forming regions in the emission line maps match very well with the regions having significant UV flux. The central regions of two galaxies (JW39, JO194) show a reduction in UV flux which coincides with composite or LINER regions in the emission line maps. The galaxies studied here demonstrate significant star formation in the stripped tails, suppressed star formation in the central regions and present a possible case of accelerated quenching happening in jellyfish galaxies.
Antibiotic Cycling Affects Resistance Evolution Independently of Collateral Sensitivity
Authors: Brepoels Pauline , Appermans Kenny , Pérez-Romero Camilo Andres , Lories Bram , Marchal Kathleen , Steenackers Hans P 
Published: December 2022

AbstractAntibiotic cycling has been proposed as a promising approach to slow down resistance evolution against currently employed antibiotics. It remains unclear, however, to which extent the decreased resistance evolution is the result of collateral sensitivity, an evolutionary trade-off where resistance to one antibiotic enhances the sensitivity to the second, or due to additional effects of the evolved genetic background, in which mutations accumulated during treatment with a first antibiotic alter the emergence and spread of resistance against a second antibiotic via other mechanisms. Also, the influence of antibiotic exposure patterns on the outcome of drug cycling is unknown. Here, we systematically assessed the effects of the evolved genetic background by focusing on the first switch between two antibiotics against Salmonella Typhimurium, with cefotaxime fixed as the first and a broad variety of other drugs as the second antibiotic. By normalizing the antibiotic concentrations to eliminate the effects of collateral sensitivity, we demonstrated a clear contribution of the evolved genetic background beyond collateral sensitivity, which either enhanced or reduced the adaptive potential depending on the specific drug combination. We further demonstrated that the gradient strength with which cefotaxime was applied affected both cefotaxime resistance evolution and adaptation to second antibiotics, an effect that was associated with higher levels of clonal interference and reduced cost of resistance in populations evolved under weaker cefotaxime gradients. Overall, our work highlights that drug cycling can affect resistance evolution independently of collateral sensitivity, in a manner that is contingent on the antibiotic exposure pattern.
Ecology, Not Host Phylogeny, Shapes the Oral Microbiome in Closely Related Species
Authors: Moraitou Markella , Forsythe Adrian , Fellows Yates James A , Brealey Jaelle C , Warinner Christina , Guschanski Katerina 
Published: December 2022

AbstractHost-associated microbiomes are essential for a multitude of biological processes. Placed at the contact zone between external and internal environments, the little-studied oral microbiome has important roles in host physiology and health. Here, we investigate the roles of host evolutionary relationships and ecology in shaping the oral microbiome in three closely related gorilla subspecies (mountain, Grauer's, and western lowland gorillas) using shotgun metagenomics of 46 museum-preserved dental calculus samples. We find that the oral microbiomes of mountain gorillas are functionally and taxonomically distinct from the other two subspecies, despite close evolutionary relationships and geographic proximity with Grauer's gorillas. Grauer's gorillas show intermediate bacterial taxonomic and functional, and dietary profiles. Altitudinal differences in gorilla subspecies ranges appear to explain these patterns, suggesting a close connection between dental calculus microbiomes and the environment, likely mediated through diet. This is further supported by the presence of gorilla subspecies-specific phyllosphere/rhizosphere taxa in the oral microbiome. Mountain gorillas show a high abundance of nitrate-reducing oral taxa, which may promote adaptation to a high-altitude lifestyle by modulating blood pressure. Our results suggest that ecology, rather than evolutionary relationships and geographic distribution, shape the oral microbiome in these closely related species.
In vivo promotion of primordial follicle activation by stem cell factor treatment in mice with premature ovarian insufficiency and advanced age
Authors: Wang Yibo , Zhang Jiawei , Liang Jing , Jia Longzhong , Niu Shudong , Cheng Kaixin , Yang Chen , Lu Zining , Mu Lu , Yang Xuebing , Zhang Yan , Zhang Hua 
Published: December 2022

Abstract
Dormant primordial follicles (PFs) are the most abundant reproductive resource in mammalian ovaries. With advances in the mechanism of study of the regulation of PF activation, PFs have been used to improve fertility in clinical practice. As a central controlling element of follicle activation signaling, the pre-granulosa cell-secreted stem cell factor (SCF; also known as KIT ligand, KITL), which initiates the growth of dormant oocytes, is an ideal natural activator that stimulates follicle activation. However, no systematic study has been conducted to identify the activating effect of SCF in vivo and in vitro. In this study, by combining an in vitro whole ovary culture system and several mouse models, we provide a series of experimental evidence that SCF is an efficient activator for improving PF activation in mouse ovaries. Our in vitro study showed that SCF increased phosphatidylinositol 3-kinase (PI3K) signaling and PF activation ratio in neonatal ovaries. In vivo ovarian non-invasive topical administrations of SCF to the ovaries efficiently improved follicle activation and development, oocyte retrieval ratio and fertility in inducible premature ovarian insufficiency mouse models and aged mice. Our study suggests that SCF is an efficient growth factor that can be applied to improve PF activation.
NrnA is a 5′-3′ exonuclease that processes short RNA substrates in vivo and in vitro
Authors: Weiss Cordelia A , Myers Tanner M , Wu Chih Hao , Jenkins Conor , Sondermann Holger , Lee Vincent T , Winkler Wade C 
Published: December 2022

Abstract
Bacterial RNases process RNAs until only short oligomers (2–5 nucleotides) remain, which are then processed by one or more specialized enzymes until only nucleoside monophosphates remain. Oligoribonuclease (Orn) is an essential enzyme that acts in this capacity. However, many bacteria do not encode for Orn and instead encode for NanoRNase A (NrnA). Yet, the catalytic mechanism, cellular roles and physiologically relevant substrates have not been fully resolved for NrnA proteins. We herein utilized a common set of reaction assays to directly compare substrate preferences exhibited by NrnA-like proteins from Bacillus subtilis, Enterococcus faecalis, Streptococcus pyogenes and Mycobacterium tuberculosis. While the M. tuberculosis protein specifically cleaved cyclic di-adenosine monophosphate, the B. subtilis, E. faecalis and S. pyogenes NrnA-like proteins uniformly exhibited striking preference for short RNAs between 2–4 nucleotides in length, all of which were processed from their 5′ terminus. Correspondingly, deletion of B. subtilis nrnA led to accumulation of RNAs between 2 and 4 nucleotides in length in cellular extracts. Together, these data suggest that many Firmicutes NrnA-like proteins are likely to resemble B. subtilis NrnA to act as a housekeeping enzyme for processing of RNAs between 2 and 4 nucleotides in length.
KLF4 inhibits early neural differentiation of ESCs by coordinating specific 3D chromatin structure
Authors: Bi Jinfang , Wang Wenbin , Zhang Meng , Zhang Baoying , Liu Man , Su Guangsong , Chen Fuquan , Chen Bohan , Shi Tengfei , Zheng Yaoqiang , Zhao Xueyuan , Zhao Zhongfang , Shi Jiandang , Li Peng , Zhang Lei , Lu Wange 
Published: December 2022

AbstractNeural differentiation of embryonic stem cells (ESCs) requires precisely orchestrated gene regulation, a process governed in part by changes in 3D chromatin structure. How these changes regulate gene expression in this context remains unclear. In this study, we observed enrichment of the transcription factor KLF4 at some poised or closed enhancers at TSS-linked regions of genes associated with neural differentiation. Combination analysis of ChIP, HiChIP and RNA-seq data indicated that KLF4 loss in ESCs induced changes in 3D chromatin structure, including increased chromatin interaction loops between neural differentiation-associated genes and active enhancers, leading to upregulated expression of neural differentiation-associated genes and therefore early neural differentiation. This study suggests KLF4 inhibits early neural differentiation by regulation of 3D chromatin structure, which is a new mechanism of early neural differentiation.
5-Methyl-cytosine stabilizes DNA but hinders DNA hybridization revealed by magnetic tweezers and simulations
Authors: Zhao Xiao-Cong , Dong Hai-Long , Li Xiao-Lu , Yang Hong-Yu , Chen Xue-Feng , Dai Liang , Wu Wen-Qiang , Tan Zhi-Jie , Zhang Xing-Hua 
Published: December 2022

Abstract
5-Methyl-cytosine (5mC) is one of the most important DNA modifications and plays versatile biological roles. It is well known that 5mC stabilizes DNA duplexes. However, it remains unclear how 5mC affects the kinetics of DNA melting and hybridization. Here, we studied the kinetics of unzipping and rezipping using a 502-bp DNA hairpin by single-molecule magnetic tweezers. Under constant loading rates, 5mC increases the unzipping force but counterintuitively decreases the rezipping force at various salt and temperature conditions. Under constant forces, the non-methylated DNA hops between metastable states during unzipping and rezipping, which implies low energy barriers. Surprisingly, the 5mC DNA can’t rezip after fully unzipping unless much lower forces are applied, where it rezips stochastically in a one-step manner, which implies 5mC kinetically hinders DNA hybridization and high energy barriers in DNA hybridization. All-atom molecular dynamics simulations reveal that the 5mC kinetically hinders DNA hybridization due to steric effects rather than electrostatic effects caused by the additional methyl groups of cytosines. Considering the possible high speed of DNA unzipping and zipping during replication and transcription, our findings provide new insights into the biological roles of 5mC.
Hierarchical DNA branch assembly-encoded fluorescent nanoladders for single-cell transcripts imaging
Authors: Cao Xiaowen , Chen Feng , Xue Jing , Zhao Yue , Bai Min , Zhao Yongxi 
Published: December 2022

AbstractSpatial visualization of single-cell transcripts is limited by signal specificity and multiplexing. Here, we report hierarchical DNA branch assembly-encoded fluorescent nanoladders, which achieve denoised and highly multiplexed signal amplification for single-molecule transcript imaging. This method first offers independent RNA-primed rolling circle amplification without nonspecific amplification based on circular DNAzyme. It then executes programmable DNA branch assembly on these amplicons to encode virtual signals for visualizing numbers of targets by FISH. In theory, more virtual signals can be encoded via the increase of detection spectral channels and repeats of the same sequences on barcode. Our method almost eliminates nonspecific amplification in fixed cells (reducing nonspecific spots of single cells from 16 to nearly zero), and achieves simultaneous quantitation of nine transcripts by using only two detection spectral channels. We demonstrate accurate RNA profiling in different cancer cells, and reveal diverse localization patterns for spatial regulation of transcripts.
Structural transitions during the cooperative assembly of baculovirus single-stranded DNA-binding protein on ssDNA
Authors: Yin Jiayi , Fu Yan , Rao Guibo , Li Zhiqiang , Tian Kexing , Chong Tingting , Kuang Kai , Wang Manli , Hu Zhihong , Cao Sheng 
Published: December 2022

Abstract
Single-stranded DNA-binding proteins (SSBs) interact with single-stranded DNA (ssDNA) to form filamentous structures with various degrees of cooperativity, as a result of intermolecular interactions between neighboring SSB subunits on ssDNA. However, it is still challenging to perform structural studies on SSB–ssDNA filaments at high resolution using the most studied SSB models, largely due to the intrinsic flexibility of these nucleoprotein complexes. In this study, HaLEF-3, an SSB protein from Helicoverpa armigera nucleopolyhedrovirus, was used for in vitro assembly of SSB–ssDNA filaments, which were structurally studied at atomic resolution using cryo-electron microscopy. Combined with the crystal structure of ssDNA-free HaLEF-3 octamers, our results revealed that the three-dimensional rearrangement of HaLEF-3 induced by an internal hinge-bending movement is essential for the formation of helical SSB–ssDNA complexes, while the contacting interface between adjacent HaLEF-3 subunits remains basically intact. We proposed a local cooperative SSB–ssDNA binding model, in which, triggered by exposure to oligonucleotides, HaLEF-3 molecules undergo ring-to-helix transition to initiate continuous SSB–SSB interactions along ssDNA. Unique structural features revealed by the assembly of HaLEF-3 on ssDNA suggest that HaLEF-3 may represent a new class of SSB.
Salmonella antibacterial Rhs polymorphic toxin inhibits translation through ADP-ribosylation of EF-Tu P-loop
Authors: Jurėnas Dukas , Rey Martial , Byrne Deborah , Chamot-Rooke Julia , Terradot Laurent , Cascales Eric 
Published: December 2022

Abstract
Rearrangement hot spot (Rhs) proteins are members of the broad family of polymorphic toxins. Polymorphic toxins are modular proteins composed of an N-terminal region that specifies their mode of secretion into the medium or into the target cell, a central delivery module, and a C-terminal domain that has toxic activity. Here, we structurally and functionally characterize the C-terminal toxic domain of the antibacterial Rhsmain protein, TreTu, which is delivered by the type VI secretion system of Salmonella enterica Typhimurium. We show that this domain adopts an ADP-ribosyltransferase fold and inhibits protein synthesis by transferring an ADP-ribose group from NAD+ to the elongation factor Tu (EF-Tu). This modification is specifically placed on the side chain of the conserved D21 residue located on the P-loop of the EF-Tu G-domain. Finally, we demonstrate that the TriTu immunity protein neutralizes TreTu activity by acting like a lid that closes the catalytic site and traps the NAD+.
Science battles viral diseases: a roundtable discussion with leading experts on COVID-19, hepatitis and AIDS
Authors: Zhu He 
Published: December 2022

ABSTRACT
The Science Popularization and Education Committee of the Academic Divisions of the Chinese Academy of Sciences (CASAD) invited the CAS Institutes of Science and Development (CASISD) and National Science Review (NSR) to organize a roundtable discussion of viral infectious diseases on 11 October 2022. During this extensive discussion, experts introduced the history and background of virus and viral infectious diseases. They explained the function of human's immune system. In addition, they answered frequently asked questions by the public such as the efficacy and safety of COVID vaccines, the cost of disease treatment and the threat of latest monkey pox outbreak.

Chen Dong (董晨)
Professor, director of Shanghai Immune Therapy Institute

Fu-Sheng Wang (王福生)
MD., director of the Department of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases

George Fu Gao (高福)
Professor, former director-general of Chinese Center for Disease Control and Prevention (China CDC)

Zhonghe Zhou (周忠和, Chair)
Associate director of the Science Popularization and Education Committee of CASAD, professor of CAS Institute of Vertebrate Paleontology and Paleoanthropology and associate editor-in-chief of NSR

Yiming Shao (邵一鸣)
Professor, deputy director of State Key Laboratory for Infectious Disease Control and Prevention, former chief expert on AIDS, China CDC