bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrative analysis of multiple genomic data from intrahepatic cholangiocarcinoma organoids enables tumor subtyping
Authors: Lee Hee Seung , Han Dai Hoon , Cho Kyungjoo , Park Soo Been , Kim Chanyang , Leem Galam , Jung Dawoon E. , Kwon Soon Sung , Kim Chul Hoon , Jo Jung Hyun , Lee Hye Won , Song Si Young , Park Jun Yong 
Published: January 2023

AbstractAs genomic analysis technology has advanced, it has become possible to sub-classify intrahepatic cholangiocarcinoma (ICC) at the histological or molecular level. Here, we verify the recently suggested two subgroups of ICC in the organoids model, compare the characteristics between types. ICC patients are subclassified into small-duct (SD) and large-duct (LD) subtype according to histological characteristics. ICC organoids are established, and unsupervised principal component analysis clustering separates each type of ICC. Differential gene expression reveals enrichment on KRAS, TGFβ and ERBB2 signaling pathways in LD-type compared with SD-type (P < 0.05). Gene set enrichment analysis demonstrates that the cholangiocarcinoma class 2 signature, defined by Andersen et al., is enriched in the LD-type (enrichment Score = 2.19, P < 0.001). A protein-protein interaction network analysis identifies ZNF217 as a significant hub protein (odds ratio = 4.96, P = 0.0105). We perform prospective modeling of histological subtype using patient-derived organoids. Moreover, gene expression profiling of ICC organoids enables identification of type-specific targetable pathways.
Inhibiting myostatin signaling partially mitigates structural and functional adaptations to hindlimb suspension in mice
Authors: Hanson Andrea M. , Young Mary H. , Harrison Brooke C. , Zhou Xiaolan , Han H. Q. , Stodieck Louis S. , Ferguson Virginia L. 
Published: January 2023

AbstractNovel treatments for muscle wasting are of significant value to patients with disease states that result in muscle weakness, injury recovery after immobilization and bed rest, and for astronauts participating in long-duration spaceflight. We utilized an anti-myostatin peptibody to evaluate how myostatin signaling contributes to muscle loss in hindlimb suspension. Male C57BL/6 mice were left non-suspended (NS) or were hindlimb suspended (HS) for 14 days and treated with a placebo vehicle (P) or anti-myostatin peptibody (D). Hindlimb suspension (HS-P) resulted in rapid and significantly decreased body mass (−5.6% by day 13) with hindlimb skeletal muscle mass losses between −11.2% and −22.5% and treatment with myostatin inhibitor (HS-D) partially attenuated these losses. Myostatin inhibition increased hindlimb strength with no effect on soleus tetanic strength. Soleus mass and fiber CSA were reduced with suspension and did not increase with myostatin inhibition. In contrast, the gastrocnemius showed histological evidence of wasting with suspension that was partially mitigated with myostatin inhibition. While expression of genes related to protein degradation (Atrogin-1 and Murf-1) in the tibialis anterior increased with suspension, these atrogenes were not significantly reduced by myostatin inhibition despite a modest activation of the Akt/mTOR pathway. Taken together, these findings suggest that myostatin is important in hindlimb suspension but also motivates the study of other factors that contribute to disuse muscle wasting. Myostatin inhibition benefitted skeletal muscle size and function, which suggests therapeutic potential for both spaceflight and terrestrial applications.
Diffusion in liquid mixtures
Authors: Vailati A. , Bataller H. , Bou-Ali M. M. , Carpineti M. , Cerbino R. , Croccolo F. , Egelhaaf S. U. , Giavazzi F. , Giraudet C. , Guevara-Carrion G. , Horváth D. , Köhler W. , Mialdun A. , Porter J. , Schwarzenberger K. , Shevtsova V. , De Wit A. 
Published: January 2023

AbstractThe understanding of transport and mixing in fluids in the presence and in the absence of external fields and reactions represents a challenging topic of strategic relevance for space exploration. Indeed, mixing and transport of components in a fluid are especially important during long-term space missions where fuels, food and other materials, needed for the sustainability of long space travels, must be processed under microgravity conditions. So far, the processes of transport and mixing have been investigated mainly at the macroscopic and microscopic scale. Their investigation at the mesoscopic scale is becoming increasingly important for the understanding of mass transfer in confined systems, such as porous media, biological systems and microfluidic systems. Microgravity conditions will provide the opportunity to analyze the effect of external fields and reactions on optimizing mixing and transport in the absence of the convective flows induced by buoyancy on Earth. This would be of great practical applicative relevance to handle complex fluids under microgravity conditions for the processing of materials in space.
Dynamic physiological α-synuclein S129 phosphorylation is driven by neuronal activity
Authors: Ramalingam Nagendran , Jin Shan-Xue , Moors Tim E. , Fonseca-Ornelas Luis , Shimanaka Kazuma , Lei Shi , Cam Hugh P. , Watson Aurelia Hays , Brontesi Lisa , Ding Lai , Hacibaloglu Dinc Yasat , Jiang Haiyang , Choi Se Joon , Kanter Ellen , Liu Lei , Bartels Tim , Nuber Silke , Sulzer David , Mosharov Eugene V. , Chen Weisheng V. , Li Shaomin , Selkoe Dennis J. , Dettmer Ulf 
Published: January 2023

AbstractIn Parkinson’s disease and other synucleinopathies, the elevation of α-synuclein phosphorylated at Serine129 (pS129) is a widely cited marker of pathology. However, the physiological role for pS129 has remained undefined. Here we use multiple approaches to show for the first time that pS129 functions as a physiological regulator of neuronal activity. Neuronal activity triggers a sustained increase of pS129 in cultured neurons (200% within 4 h). In accord, brain pS129 is elevated in environmentally enriched mice exhibiting enhanced long-term potentiation. Activity-dependent α-synuclein phosphorylation is S129-specific, reversible, confers no cytotoxicity, and accumulates at synapsin-containing presynaptic boutons. Mechanistically, our findings are consistent with a model in which neuronal stimulation enhances Plk2 kinase activity via a calcium/calcineurin pathway to counteract PP2A phosphatase activity for efficient phosphorylation of membrane-bound α-synuclein. Patch clamping of rat SNCA−/− neurons expressing exogenous wild-type or phospho-incompetent (S129A) α-synuclein suggests that pS129 fine-tunes the balance between excitatory and inhibitory neuronal currents. Consistently, our novel S129A knock-in (S129AKI) mice exhibit impaired hippocampal plasticity. The discovery of a key physiological function for pS129 has implications for understanding the role of α-synuclein in neurotransmission and adds nuance to the interpretation of pS129 as a synucleinopathy biomarker.
A topographic atlas defines developmental origins of cell heterogeneity in the human embryonic lung
Authors: Sountoulidis Alexandros , Marco Salas Sergio , Braun Emelie , Avenel Christophe , Bergenstråhle Joseph , Theelke Jonas , Vicari Marco , Czarnewski Paulo , Liontos Andreas , Abalo Xesus , Andrusivová Žaneta , Mirzazadeh Reza , Asp Michaela , Li Xiaofei , Hu Lijuan , Sariyar Sanem , Martinez Casals Anna , Ayoglu Burcu , Firsova Alexandra , Michaëlsson Jakob , Lundberg Emma , Wählby Carolina , Sundström Erik , Linnarsson Sten , Lundeberg Joakim , Nilsson Mats , Samakovlis Christos 
Published: January 2023

AbstractThe lung contains numerous specialized cell types with distinct roles in tissue function and integrity. To clarify the origins and mechanisms generating cell heterogeneity, we created a comprehensive topographic atlas of early human lung development. Here we report 83 cell states and several spatially resolved developmental trajectories and predict cell interactions within defined tissue niches. We integrated single-cell RNA sequencing and spatially resolved transcriptomics into a web-based, open platform for interactive exploration. We show distinct gene expression programmes, accompanying sequential events of cell differentiation and maturation of the secretory and neuroendocrine cell types in proximal epithelium. We define the origin of airway fibroblasts associated with airway smooth muscle in bronchovascular bundles and describe a trajectory of Schwann cell progenitors to intrinsic parasympathetic neurons controlling bronchoconstriction. Our atlas provides a rich resource for further research and a reference for defining deviations from homeostatic and repair mechanisms leading to pulmonary diseases.
Simultaneous identification of viruses and viral variants with programmable DNA nanobait
Authors: Bošković Filip , Zhu Jinbo , Tivony Ran , Ohmann Alexander , Chen Kaikai , Alawami Mohammed F. , Đorđević Milan , Ermann Niklas , Pereira-Dias Joana , Fairhead Michael , Howarth Mark , Baker Stephen , Keyser Ulrich F. 
Published: January 2023

AbstractRespiratory infections are the major cause of death from infectious disease worldwide. Multiplexed diagnostic approaches are essential as many respiratory viruses have indistinguishable symptoms. We created self-assembled DNA nanobait that can simultaneously identify multiple short RNA targets. The nanobait approach relies on specific target selection via toehold-mediated strand displacement and rapid readout via nanopore sensing. Here we show that this platform can concurrently identify several common respiratory viruses, detecting a panel of short targets of viral nucleic acids from multiple viruses. Our nanobait can be easily reprogrammed to discriminate viral variants with single-nucleotide resolution, as we demonstrated for several key SARS-CoV-2 variants. Last, we show that the nanobait discriminates between samples extracted from oropharyngeal swabs from negative- and positive-SARS-CoV-2 patients without preamplification. Our system allows for the multiplexed identification of native RNA molecules, providing a new scalable approach for the diagnostics of multiple respiratory viruses in a single assay.
A structural basis for prion strain diversity
Authors: Manka Szymon W. , Wenborn Adam , Betts Jemma , Joiner Susan , Saibil Helen R. , Collinge John , Wadsworth Jonathan D. F. 
Published: January 2023

AbstractRecent cryogenic electron microscopy (cryo-EM) studies of infectious, ex vivo, prion fibrils from hamster 263K and mouse RML prion strains revealed a similar, parallel in-register intermolecular β-sheet (PIRIBS) amyloid architecture. Rungs of the fibrils are composed of individual prion protein (PrP) monomers that fold to create distinct N-terminal and C-terminal lobes. However, disparity in the hamster/mouse PrP sequence precludes understanding of how divergent prion strains emerge from an identical PrP substrate. In this study, we determined the near-atomic resolution cryo-EM structure of infectious, ex vivo mouse prion fibrils from the ME7 prion strain and compared this with the RML fibril structure. This structural comparison of two biologically distinct mouse-adapted prion strains suggests defined folding subdomains of PrP rungs and the way in which they are interrelated, providing a structural definition of intra-species prion strain-specific conformations.
ELI trifocal microscope: a precise system to prepare target cryo-lamellae for in situ cryo-ET study
Authors: Li Shuoguo , Wang Ziyan , Jia Xing , Niu Tongxin , Zhang Jianguo , Yin Guoliang , Zhang Xiaoyun , Zhu Yun , Ji Gang , Sun Fei 
Published: January 2023

AbstractCryo-electron tomography (cryo-ET) has become a powerful approach to study the high-resolution structure of cellular macromolecular machines in situ. However, the current correlative cryo-fluorescence and electron microscopy lacks sufficient accuracy and efficiency to precisely prepare cryo-lamellae of target locations for subsequent cryo-ET. Here we describe a precise cryogenic fabrication system, ELI-TriScope, which sets electron (E), light (L) and ion (I) beams at the same focal point to achieve accurate and efficient preparation of a target cryo-lamella. ELI-TriScope uses a commercial dual-beam scanning electron microscope modified to incorporate a cryo-holder-based transfer system and embed an optical imaging system just underneath the vitrified specimen. Cryo-focused ion beam milling can be accurately navigated by monitoring the real-time fluorescence signal of the target molecule. Using ELI-TriScope, we prepared a batch of cryo-lamellae of HeLa cells targeting the centrosome with a success rate of ~91% and discovered new in situ structural features of the human centrosome by cryo-ET.
Integrated multimodality microscope for accurate and efficient target-guided cryo-lamellae preparation
Authors: Li Weixing , Lu Jing , Xiao Ke , Zhou Maoge , Li Yuanyuan , Zhang Xiang , Li Zhixun , Gu Lusheng , Xu Xiaojun , Guo Qiang , Xu Tao , Ji Wei 
Published: January 2023

AbstractCryo-electron tomography (cryo-ET) is a revolutionary technique for resolving the structure of subcellular organelles and macromolecular complexes in their cellular context. However, the application of the cryo-ET is hampered by the sample preparation step. Performing cryo-focused ion beam milling at an arbitrary position on the sample is inefficient, and the target of interest is not guaranteed to be preserved when thinning the cell from several micrometers to less than 300 nm thick. Here, we report a cryogenic correlated light, ion and electron microscopy (cryo-CLIEM) technique that is capable of preparing cryo-lamellae under the guidance of three-dimensional confocal imaging. Moreover, we demonstrate a workflow to preselect and preserve nanoscale target regions inside the finished cryo-lamellae. By successfully preparing cryo-lamellae that contain a single centriole or contact sites between subcellular organelles, we show that this approach is generally applicable, and shall help in innovating more applications of cryo-ET.
Polygenic risk score for tumor aggressiveness and early-onset prostate cancer in Asians
Authors: Song Sang Hun , Kim Eunae , Jung Yu Jin , Kim Hak-Min , Park Moon Soo , Kim Jung Kwon , Lee Hakmin , Oh Jong Jin , Lee Sangchul , Hong Sung Kyu , Byun Seok-Soo 
Published: January 2023

AbstractWe attempted to assess the performance of an ethnic-specific polygenic risk score (PRS) designed from a Korean population to predict aggressive prostate cancer (PCa) and early-onset (age < 60). A PRS score comprised of 22 SNPs was computed in 3695 patients gathered from one of 4 tertiary centers in Korea. Males with biopsy or radical prostatectomy-proven PCa were included for analysis, collecting additional clinical parameters such as age, BMI, PSA, Gleason Group (GG), and staging. Patients were divided into 4 groups of PRS quartiles. Intergroup differences were assessed, as well as risk ratio and predictive performance based on GG using logistic regression analysis and AUC. No significant intergroup differences were observed for BMI, PSA, and rate of ≥ T3a tumors on pathology. Rate of GG ≥ 2, GG ≥ 3, and GG ≥ 4 showed a significant pattern of increase by PRS quartile (p < 0.001, < 0.001, and 0.039, respectively). With the lowest PRS quartile as reference, higher PRS groups showed sequentially escalating risk for GG ≥ 2 and GG ≥ 3 pathology, with a 4.6-fold rise in GG ≥ 2 (p < 0.001) and 2.0-fold rise in GG ≥ 3 (p < 0.001) for the highest PRS quartiles. Combining PRS with PSA improved prediction of early onset csPCa (AUC 0.759) compared to PRS (AUC 0.627) and PSA alone (AUC 0.736). To conclude, an ethnic-specific PRS was found to predict susceptibility of aggressive PCa in addition to improving detection of csPCa when combined with PSA in early onset populations. PRS may have a role as a risk-stratification model in actual practice. Large scale, multi-ethnic trials are required to validate our results.
A bolder conservation future for Indonesia by prioritising biodiversity, carbon and unique ecosystems in Sulawesi
Authors: Pusparini Wulan , Cahyana Andi , Grantham Hedley S. , Maxwell Sean , Soto-Navarro Carolina , Macdonald David W. 
Published: January 2023

AbstractAs more ambitious protected area (PA) targets for the post-2020 global biodiversity framework are set beyond Aichi Target 11, renew thinking into spatial prioritisation is required to enable PA expansion that maximises environmental values. Our study focuses on the biodiverse and forest-rich Indonesian island of Sulawesi, which has a terrestrial PA network that covers 10% of the island. We used Marxan to investigate trade-offs in the design of an expanded PA network that prioritised different conservation features (biodiversity, forest cover, carbon stock, karst and valuable metal-rich areas) under varying island-wide coverage targets (17%, 30%, and 50%). Our first scenario, which required existing PAs to be selected, required larger areas to meet these coverage targets, in contrast to our second scenario, which allowed for any part of the island to be chosen, irrespective of PA status. The vast Mekongga and Bangkiriang Landscapes, and Gorontalo corridor were consistently identified as a high priority for protection under all scenarios. To meet our conservation targets through expanding current PAs, creating new PAs, and creating corridors that connect existing PAs, we used a spatially explicit three-phase approach. Our findings identified 26,508 km2of priority areas to be included in the current PA network, potentially assisting Indonesia in meeting its post-2020 GBF target, if our approach is replicated across Indonesia as a national or sub-national analysis. We discuss various land management options through other effective area-based conservation measures (OECMs) and the costs to deliver this strategy.
Looking at faces in the wild
Authors: Varela Victor P. L. , Towler Alice , Kemp Richard I. , White David 
Published: January 2023

AbstractFaces are key to everyday social interactions, but our understanding of social attention is based on experiments that present images of faces on computer screens. Advances in wearable eye-tracking devices now enable studies in unconstrained natural settings but this approach has been limited by manual coding of fixations. Here we introduce an automatic ‘dynamic region of interest’ approach that registers eye-fixations to bodies and faces seen while a participant moves through the environment. We show that just 14% of fixations are to faces of passersby, contrasting with prior screen-based studies that suggest faces automatically capture visual attention. We also demonstrate the potential for this new tool to help understand differences in individuals’ social attention, and the content of their perceptual exposure to other people. Together, this can form the basis of a new paradigm for studying social attention ‘in the wild’ that opens new avenues for theoretical, applied and clinical research.
Carcass traits and meat quality of goats fed with cactus pear (Opuntia ficus-indica Mill) silage subjected to an intermittent water supply
Authors: de Lima Cruz Gabriel Ferreira , Santos Edson Mauro , de Araújo Gherman Garcia Leal , de Azevedo Paulo Sérgio , de Albuquerque Ítalo Reneu Rosas , Panosso Natália Matos , Perazzo Alexandre Fernandes , de Moura Zanine Anderson , de Jesus Ferreira Daniele , de Oliveira Lima Anny Graycy Vasconcelos , de Oliveira Juliana Silva 
Published: January 2023

AbstractThe effect of different proportions of cactus pear (Opuntia ficus-indica Mill) silage (CPS) and intermittent water supply (IWS) to crossbreed goats' diets on carcass traits and meat quality were evaluated. The IWS caused a reduction (p = 0.03) in the percentage of leg fat in the animals. The rib eye area, carcass weight, and physical–chemical characteristics were not affected (p > 0.05) by the CPS or IWS. The IWS reduced (p = 0.04) the elongase enzyme activity. The CPS inclusion in the diet reduced C22:0 (p = 0.01), some branched-chain fatty acid (BCFA), C20:1 (p = 0.03), c13-C18:1 (p = 0.01) fatty acids. Therefore, in situations of water scarcity, an intermittent water supply of up to 48 h and diets with up to 42% cactus pear silage, can be adopted in goat feedlot, without affecting carcass traits and meat quality.
Reciprocal facilitation between mental and visuomotor rotations
Authors: Guo Jianfei , Song Joo-Hyun 
Published: January 2023

AbstractHumans exhibit remarkably complex cognitive abilities and adaptive behavior in daily life. Cognitive operation in the "mental workspace," such as mentally rotating a piece of luggage to fit into fixed trunk space, helps us maintain and manipulate information on a moment-to-moment basis. Skill acquisition in the "sensorimotor workspace," such as learning a new mapping between the magnitude of new vehicle movement and wheel turn, allows us to adjust our behavior to changing environmental or internal demands to maintain appropriate motor performance. While this cognitive and sensorimotor synergy is at the root of adaptive behavior in the real world, their interplay has been understudied due to a divide-and-conquer approach. We evaluated whether a separate domain-specific or common domain-general operation drives mental and sensorimotor rotational transformations. We observed that participants improved the efficiency of mental rotation speed after the visuomotor rotation training, and their learning rate for visuomotor adaptation also improved after their mental rotation training. Such bidirectional transfer between two widely different tasks highlights the remarkable reciprocal plasticity and demonstrates a common transformation mechanism between two intertwined workspaces. Our findings urge the necessity of an explicitly integrated approach to enhance our understanding of the dynamic interdependence between cognitive and sensorimotor mechanisms.
Biogeneration of silver nanoparticles from Cuphea procumbens for biomedical and environmental applications
Authors: González-Pedroza María G. , Benítez Andrea Regina Tapia , Navarro-Marchal Saúl A. , Martínez-Martínez Eduardo , Marchal Juan A. , Boulaiz Houria , Morales-Luckie Raúl A. 
Published: January 2023

AbstractNanotechnology is one of the most important and relevant disciplines today due to the specific electrical, optical, magnetic, chemical, mechanical and biomedical properties of nanoparticles. In the present study we demonstrate the efficacy ofCuphea procumbensto biogenerate silver nanoparticles (AgNPs) with antibacterial and antitumor activity. These nanoparticles were synthesized using the aqueous extract ofC. procumbensas reducing agent and silver nitrate as oxidizing agent. The Transmission Electron Microscopy demonstrated that the biogenic AgNPs were predominantly quasi-spherical with an average particle size of 23.45 nm. The surface plasmonic resonance was analyzed by ultraviolet visible spectroscopy (UV–Vis) observing a maximum absorption band at 441 nm and Infrared Spectroscopy (FT IR) was used in order to structurally identify the functional groups of some compounds involved in the formation of nanoparticles. The AgNPs demonstrated to have antibacterial activity against the pathogenic bacteriaEscherichia coliandStaphylococcus aureus, identifying the maximum zone of inhibition at the concentration of 0.225 and 0.158 µg/mL respectively. Moreover, compared to the extract, AgNPs exhibited better antitumor activity and higher therapeutic index (TI) against several tumor cell lines such as human breast carcinoma MCF-7 (IC50of 2.56 µg/mL, TI of 27.65 µg/mL), MDA-MB-468 (IC50of 2.25 µg/mL, TI of 31.53 µg/mL), human colon carcinoma HCT-116 (IC50of 1.38 µg/mL, TI of 51.07 µg/mL) and melanoma A-375 (IC50of 6.51 µg/mL, TI of 10.89 µg/mL). This fact is of great since it will reduce the side effects derived from the treatment. In addition, AgNPs revealed to have a photocatalytic activity of the dyes congo red (10–3 M) in 5 min and malachite green (10–3 M) in 7 min. Additionally, the degradation percentages were obtained, which were 86.61% for congo red and 82.11% for malachite green. Overall, our results demonstrated for the first time thatC. procumbensbiogenerated nanoparticles are excellent candidates for several biomedical and environmental applications.