bluuebunny/crossref_metadata_2025_split huggingface dataset:
The emerging roles of circular RNA-mediated autophagy in tumorigenesis and cancer progression
Authors: Yuan Yuan , Zhang Xiaojing , Fan Xinmin , Peng Yin , Jin Zhe 
Published: September 2022

AbstractCircular RNA (circRNA) is characterized by a specific covalently closed ring structure. The back-splicing of precursor mRNA is the main way of circRNA generation, and various cis/trans-acting elements are involved in regulating the process. circRNAs exhibit multiple biological functions, including serving as sponges of microRNAs, interacting with proteins to regulate their stabilities and abilities, and acting as templates for protein translation. Autophagy participates in many physiological and pathological processes, especially it plays a vital role in tumorigenesis and carcinoma progression. Increasing numbers of evidences have revealed that circRNAs are implicated in regulating autophagy during tumor development. Until now, the roles of autophagy-associated circRNAs in carcinoma progression and their molecular mechanisms remain unclear. Here, the emerging regulatory roles and mechanisms of circRNAs in autophagy were summarized. Furtherly, the effects of autophagy-associated circRNAs on cancer development were described. We also prospected the potential of autophagy-associated circRNAs as novel therapeutic targets of tumors and as biomarkers for cancer diagnosis and prognosis.
Presenting clinical characteristics of open globe injuries in ocular trauma: baseline analysis of cases in the ASCOT national clinical trial
Authors: Cro Suzie , Partington Giles , Cornelius Victoria R. , Banerjee Philip J. , Zvobgo Tapiwa Margaret , Casswell Edward J. , Shahid Syed , Bunce Catey , Robertson Elizabeth , Murphy Caroline , Kelly Joanna , Charteris David G. 
Published: September 2022

Abstract
Background/Objectives
The Adjunctive Steroid Combination in Ocular Trauma (ASCOT) trial is a unique pragmatic, multi-centre, patient and assessor masked, randomised controlled trial. We evaluate the clinical characteristics and pathology of this large trial cohort of patients with open globe injuries undergoing vitreoretinal surgery, including the associations between patient characteristics and their baseline vision.

Subjects/Methods
We (i) summarise demographics, injury history and ocular history of the 280 participants recruited into the ASCOT trial using descriptive statistics; (ii) analyse the national and seasonal variation across England and Scotland in these participant characteristics; and (iii) explore the associations between participant demographic, trauma history, ocular history and presenting baseline visual acuity (measured using the Early Treatment Diabetic Retinopathy Study, ETDRS) using multivariable regression analyses.

Results
The majority of participants with open globe penetrating injuries were of white ethnicity (233, 84%), male (246, 88%), with a median age of 43 years (IQR 30–55 years). There was considerable variability in presenting visual acuity with 75% unable to read any letters on the ETDRS chart, whilst the median ETDRS letter score was 58 (IQR 24–80) for those who could read ≥1 letter. The most common causes of injury were workplace related (31%) or interpersonal violence (24%). Previous eye surgery, visual axis corneal scar, lens status, hyphaemia and vitreous haemorrhaging were found to be associated with presenting vision as measured by the ETDRS chart.

Conclusion
The ASCOT trial provides valuable insights into the spectrum of pathology of patients with open globe eye injuries undergoing vitreoretinal surgery. The identified causes of injury and clinical presentation of the cases will help in training and resource planning to deal with these often challenging surgical cases.

Trial registration
EudraCT No. 014-002193-37. HTA Project 12/35/64.
Characterisation of macular neovascularisation subtypes in age-related macular degeneration to optimise treatment outcomes
Authors: Mathis Thibaud , Holz Frank G. , Sivaprasad Sobha , Yoon Young Hee , Eter Nicole , Chen Lee-Jen , Koh Adrian , Cunha de Souza Eduardo , Staurenghi Giovanni 
Published: September 2022

AbstractThe aim of this review is to identify the common characteristics and prognoses of different subtypes of neovascular age-related macular degeneration (nAMD). We also propose recommendations on how to tailor treatments to the subtype of neovessels to optimise patient outcomes. The authors, selected members of the Vision Academy, met to discuss treatment outcomes in nAMD according to macular neovascularisation (MNV) subtypes, using evidence from a literature search conducted on the PubMed database (cut-off date: March 2019). This review article summarises the recommendations of the Vision Academy on how the characterisation of MNV subtypes can optimise treatment outcomes in nAMD. The identification of MNV subtypes has been facilitated by the advent of multimodal imaging. Findings from fluorescein angiography, indocyanine green angiography and spectral-domain optical coherence tomography collectively help refine and standardise the determination of the MNV subtype. To date, three subtypes have been described in the literature and have specific characteristics, as identified by imaging. Type 1 MNV is associated with better long-term outcomes but usually requires more intense anti-vascular endothelial growth factor dosing. Type 2 MNV typically responds quickly to treatment but is more prone to the development of fibrotic scars, which may be associated with poorer outcomes. Type 3 MNV tends to be highly sensitive to anti-vascular endothelial growth factor treatment but may be associated with a higher incidence of outer retinal atrophy, compared with other subtypes. Accurately assessing the MNV subtype provides information on prognosis and helps to optimise the management of patients with nAMD.
Ice mass loss sensitivity to the Antarctic ice sheet basal thermal state
Authors: Dawson Eliza J. , Schroeder Dustin M. , Chu Winnie , Mantelli Elisa , Seroussi Hélène 
Published: September 2022

AbstractSea-level rise projections rely on accurate predictions of ice mass loss from Antarctica. Climate change promotes greater mass loss by destabilizing ice shelves and accelerating the discharge of upstream grounded ice. Mass loss is further exacerbated by mechanisms such as the Marine Ice Sheet Instability and the Marine Ice Cliff Instability. However, the effect of basal thermal state changes of grounded ice remains largely unexplored. Here, we use numerical ice sheet modeling to investigate how warmer basal temperatures could affect the Antarctic ice sheet mass balance. We find increased mass loss in response to idealized basal thawing experiments run over 100 years. Most notably, frozen-bed patches could be tenuously sustaining the current ice configuration in parts of George V, Adélie, Enderby, and Kemp Land regions of East Antarctica. With less than 5 degrees of basal warming, these frozen patches may begin to thaw, producing new loci of mass loss.
The clinical drug candidate anle138b binds in a cavity of lipidic α-synuclein fibrils
Authors: Antonschmidt Leif , Matthes Dirk , Dervişoğlu Rıza , Frieg Benedikt , Dienemann Christian , Leonov Andrei , Nimerovsky Evgeny , Sant Vrinda , Ryazanov Sergey , Giese Armin , Schröder Gunnar F. , Becker Stefan , de Groot Bert L. , Griesinger Christian , Andreas Loren B. 
Published: September 2022

AbstractAggregation of amyloidogenic proteins is a characteristic of multiple neurodegenerative diseases. Atomic resolution of small molecule binding to such pathological protein aggregates is of interest for the development of therapeutics and diagnostics. Here we investigate the interaction between α-synuclein fibrils and anle138b, a clinical drug candidate for disease modifying therapy in neurodegeneration and a promising scaffold for positron emission tomography tracer design. We used nuclear magnetic resonance spectroscopy and the cryogenic electron microscopy structure of α-synuclein fibrils grown in the presence of lipids to locate anle138b within a cavity formed between two β-strands. We explored and quantified multiple binding modes of the compound in detail using molecular dynamics simulations. Our results reveal stable polar interactions between anle138b and backbone moieties inside the tubular cavity of the fibrils. Such cavities are common in other fibril structures as well.
Flying electron spin control gates
Authors: Helgers Paul L. J. , Stotz James A. H. , Sanada Haruki , Kunihashi Yoji , Biermann Klaus , Santos Paulo V. 
Published: September 2022

AbstractThe control of "flying” (or moving) spin qubits is an important functionality for the manipulation and exchange of quantum information between remote locations on a chip. Typically, gates based on electric or magnetic fields provide the necessary perturbation for their control either globally or at well-defined locations. Here, we demonstrate the dynamic control of moving electron spins via contactless gates that move together with the spins. The concept is realized using electron spins trapped and transported by moving potential dots defined by a surface acoustic wave (SAW). The SAW strain at the electron trapping site, which is set by the SAW amplitude, acts as a contactless, tunable gate that controls the precession frequency of the flying spins via the spin-orbit interaction. We show that the degree of precession control in moving dots exceeds previously reported results for unconstrained transport by an order of magnitude and is well accounted for by a theoretical model for the strain contribution to the spin-orbit interaction. This flying spin gate permits the realization of an acoustically driven optical polarization modulator based on electron spin transport, a key element for on-chip spin information processing with a photonic interface.
Structure of an MHC I–tapasin–ERp57 editing complex defines chaperone promiscuity
Authors: Müller Ines Katharina , Winter Christian , Thomas Christoph , Spaapen Robbert M. , Trowitzsch Simon , Tampé Robert 
Published: September 2022

AbstractAdaptive immunity depends on cell surface presentation of antigenic peptides by major histocompatibility complex class I (MHC I) molecules and on stringent ER quality control in the secretory pathway. The chaperone tapasin in conjunction with the oxidoreductase ERp57 is crucial for MHC I assembly and for shaping the epitope repertoire for high immunogenicity. However, how the tapasin–ERp57 complex engages MHC I clients has not yet been determined at atomic detail. Here, we present the 2.7-Å crystal structure of a tapasin–ERp57 heterodimer in complex with peptide-receptive MHC I. Our study unveils molecular details of client recognition by the multichaperone complex and highlights elements indispensable for peptide proofreading. The structure of this transient ER quality control complex provides the mechanistic basis for the selector function of tapasin and showcases how the numerous MHC I allomorphs are chaperoned during peptide loading and editing.
Streptococcus agalactiae cadD alleviates metal stress and promotes intracellular survival in macrophages and ascending infection during pregnancy
Authors: Korir Michelle L. , Doster Ryan S. , Lu Jacky , Guevara Miriam A. , Spicer Sabrina K. , Moore Rebecca E. , Francis Jamisha D. , Rogers Lisa M. , Haley Kathryn P. , Blackman Amondrea , Noble Kristen N. , Eastman Alison J. , Williams Janice A. , Damo Steven M. , Boyd Kelli L. , Townsend Steven D. , Henrique Serezani C. , Aronoff David M. , Manning Shannon D. , Gaddy Jennifer A. 
Published: September 2022

AbstractPerinatal infection with Streptococcus agalactiae, or Group B Streptococcus (GBS), is associated with preterm birth, neonatal sepsis, and stillbirth. Here, we study the interactions of GBS with macrophages, essential sentinel immune cells that defend the gravid reproductive tract. Transcriptional analyses of GBS-macrophage co-cultures reveal enhanced expression of a gene encoding a putative metal resistance determinant, cadD. Deletion of cadD reduces GBS survival in macrophages, metal efflux, and resistance to metal toxicity. In a mouse model of ascending infection during pregnancy, the ΔcadD strain displays attenuated bacterial burden, inflammation, and cytokine production in gestational tissues. Furthermore, depletion of host macrophages alters cytokine expression and decreases GBS invasion in a cadD-dependent fashion. Our results indicate that GBS cadD plays an important role in metal detoxification, which promotes immune evasion and bacterial proliferation in the pregnant host.
Telomere-to-telomere genome sequence of the model mould pathogen Aspergillus fumigatus
Authors: Bowyer Paul , Currin Andrew , Delneri Daniela , Fraczek Marcin G. 
Published: September 2022

AbstractThe pathogenic fungus Aspergillus fumigatus is a major etiological agent of fungal invasive and chronic diseases affecting tens of millions of individuals worldwide. Draft genome sequences of two clinical isolates (Af293 and A1163) are commonly used as reference genomes for analyses of clinical and environmental strains. However, the reference sequences lack coverage of centromeres, an accurate sequence for ribosomal repeats, and a comprehensive annotation of chromosomal rearrangements such as translocations and inversions. Here, we used PacBio Single Molecule Real-Time (SMRT), Oxford Nanopore and Illumina HiSeq sequencing for de novo genome assembly and polishing of two laboratory reference strains of A. fumigatus, CEA10 (parental isolate of A1163) and its descendant A1160. We generated full length chromosome assemblies and a comprehensive telomere-to-telomere coverage for CEA10 and near complete assembly of A1160 including ribosomal repeats and the sequences of centromeres, which we discovered to be composed of long transposon elements. We envision these high-quality reference genomes will become fundamental resources to study A. fumigatus biology, pathogenicity and virulence, and to discover more effective treatments against diseases caused by this fungus.
Multiple parameters shape the 3D chromatin structure of single nuclei at the doc locus in Drosophila
Authors: Götz Markus , Messina Olivier , Espinola Sergio , Fiche Jean-Bernard , Nollmann Marcelo 
Published: September 2022

AbstractThe spatial organization of chromatin at the scale of topologically associating domains (TADs) and below displays large cell-to-cell variations. Up until now, how this heterogeneity in chromatin conformation is shaped by chromatin condensation, TAD insulation, and transcription has remained mostly elusive. Here, we used Hi-M, a multiplexed DNA-FISH imaging technique providing developmental timing and transcriptional status, to show that the emergence of TADs at the ensemble level partially segregates the conformational space explored by single nuclei during the early development of Drosophila embryos. Surprisingly, a substantial fraction of nuclei display strong insulation even before TADs emerge. Moreover, active transcription within a TAD leads to minor changes to the local inter- and intra-TAD chromatin conformation in single nuclei and only weakly affects insulation to the neighboring TAD. Overall, our results indicate that multiple parameters contribute to shaping the chromatin architecture of single nuclei at the TAD scale.
Structural basis for APE1 processing DNA damage in the nucleosome
Authors: Weaver Tyler M. , Hoitsma Nicole M. , Spencer Jonah J. , Gakhar Lokesh , Schnicker Nicholas J. , Freudenthal Bret D. 
Published: September 2022

AbstractGenomic DNA is continually exposed to endogenous and exogenous factors that promote DNA damage. Eukaryotic genomic DNA is packaged into nucleosomes, which present a barrier to accessing and effectively repairing DNA damage. The mechanisms by which DNA repair proteins overcome this barrier to repair DNA damage in the nucleosome and protect genomic stability is unknown. Here, we determine how the base excision repair (BER) endonuclease AP-endonuclease 1 (APE1) recognizes and cleaves DNA damage in the nucleosome. Kinetic assays determine that APE1 cleaves solvent-exposed AP sites in the nucleosome with 3 − 6 orders of magnitude higher efficiency than occluded AP sites. A cryo-electron microscopy structure of APE1 bound to a nucleosome containing a solvent-exposed AP site reveal that APE1 uses a DNA sculpting mechanism for AP site recognition, where APE1 bends the nucleosomal DNA to access the AP site. Notably, additional biochemical and structural characterization of occluded AP sites identify contacts between the nucleosomal DNA and histone octamer that prevent efficient processing of the AP site by APE1. These findings provide a rationale for the position-dependent activity of BER proteins in the nucleosome and suggests the ability of BER proteins to sculpt nucleosomal DNA drives efficient BER in chromatin.
Decoupled Asian monsoon intensity and precipitation during glacial-interglacial transitions on the Chinese Loess Plateau
Authors: Zheng Yukun , Liu Hongyan , Yang Huan , Wang Hongya , Zhao Wenjie , Zhang Zeyu , Huang Miao , Liu Weihang 
Published: September 2022

AbstractThe discrepancies among the variations in global ice volume, cave stalagmite δ18O and rainfall reconstructed by cosmogenic 10Be tremendously restrain our understanding of the evolution of the East Asian summer monsoon (EASM). Here, we present a 430-ka EASM mean annual precipitation record on the Chinese Loess Plateau obtained using branched glycerol dialkyl glycerol tetraethers based on a deep learning neural network; this rainfall record corresponds well with cave-derived δ18O data from southern China but differs from precipitation reconstructed by 10Be. Both branched tetraether membrane lipids and cave δ18O may be affected by soil moisture and atmospheric temperature when glacial and interglacial conditions alternated and were thus decoupled from atmospheric precipitation; instead, they represent variations in the intensity of the EASM. Furthermore, we demonstrate that the brGDGT-DLNN method can significantly extend the temporal scale record of the EASM and is not restricted by geographic location compared with stalagmite records.
Optogenetic control of apical constriction induces synthetic morphogenesis in mammalian tissues
Authors: Martínez-Ara Guillermo , Taberner Núria , Takayama Mami , Sandaltzopoulou Elissavet , Villava Casandra E. , Bosch-Padrós Miquel , Takata Nozomu , Trepat Xavier , Eiraku Mototsugu , Ebisuya Miki 
Published: September 2022

AbstractThe emerging field of synthetic developmental biology proposes bottom-up approaches to examine the contribution of each cellular process to complex morphogenesis. However, the shortage of tools to manipulate three-dimensional (3D) shapes of mammalian tissues hinders the progress of the field. Here we report the development of OptoShroom3, an optogenetic tool that achieves fast spatiotemporal control of apical constriction in mammalian epithelia. Activation of OptoShroom3 through illumination in an epithelial Madin-Darby Canine Kidney (MDCK) cell sheet reduces the apical surface of the stimulated cells and causes displacements in the adjacent regions. Light-induced apical constriction provokes the folding of epithelial cell colonies on soft gels. Its application to murine and human neural organoids leads to thickening of neuroepithelia, apical lumen reduction in optic vesicles, and flattening in neuroectodermal tissues. These results show that spatiotemporal control of apical constriction can trigger several types of 3D deformation depending on the initial tissue context.
Cancer co-opts differentiation of B-cell precursors into macrophage-like cells
Authors: Chen Chen , Park Bongsoo , Ragonnaud Emeline , Bodogai Monica , Wang Xin , Zong Le , Lee Jung-Min , Beerman Isabel , Biragyn Arya 
Published: September 2022

AbstractWe have recently reported that some cancers induce accumulation of bone marrow (BM) B-cell precursors in the spleen to convert them into metastasis-promoting, immunosuppressive B cells. Here, using various murine tumor models and samples from humans with breast and ovarian cancers, we provide evidence that cancers also co-opt differentiation of these B-cell precursors to generate macrophage-like cells (termed B-MF). We link the transdifferentiation to a small subset of CSF1R+ Pax5Low cells within BM pre-B and immature B cells responding to cancer-secreted M-CSF with downregulation of the transcription factor Pax5 via CSF1R signaling. Although the primary source of tumor-associated macrophages is monocytes, B-MFs are phenotypically and functionally distinguishable. Compared to monocyte-derived macrophages, B-MFs more efficiently phagocytize apoptotic cells, suppress proliferation of T cells and induce FoxP3+ regulatory T cells. In mouse tumor models, B-MFs promote shrinkage of the tumor-infiltrating IFNγ+ CD4 T cell pool and increase cancer progression and metastasis, suggesting that this cancer-induced transdifferentiation pathway is functionally relevant and hence could serve as an immunotherapeutic target.
Assembly of transmembrane pores from mirror-image peptides
Authors: Krishnan R Smrithi , Jana Kalyanashis , Shaji Amina H. , Nair Karthika S. , Das Anjali Devi , Vikraman Devika , Bajaj Harsha , Kleinekathöfer Ulrich , Mahendran Kozhinjampara R. 
Published: September 2022

AbstractTailored transmembrane alpha-helical pores with desired structural and functional versatility have promising applications in nanobiotechnology. Herein, we present a transmembrane pore DpPorA, based on the natural pore PorACj, built from D-amino acid α-helical peptides. Using single-channel current recordings, we show that DpPorA peptides self-assemble into uniform cation-selective pores in lipid membranes and exhibit properties distinct from their L-amino acid counterparts. DpPorA shows resistance to protease and acts as a functional nanopore sensor to detect cyclic sugars, polypeptides, and polymers. Fluorescence imaging reveals that DpPorA forms well-defined pores in giant unilamellar vesicles facilitating the transport of hydrophilic molecules. A second D-amino acid peptide based on the polysaccharide transporter Wza forms transient pores confirming sequence specificity in stable, functional pore formation. Finally, molecular dynamics simulations reveal the specific alpha-helical packing and surface charge conformation of the D-pores consistent with experimental observations. Our findings will aid the design of sophisticated pores for single-molecule sensing related technologies.