bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell-type-specific epigenetic effects of early life stress on the brain
Authors: Rahman Mouly F. , McGowan Patrick O. 
Published: August 2022

AbstractEarly life stress (ELS) induces long-term phenotypic adaptations that contribute to increased vulnerability to a host of neuropsychiatric disorders. Epigenetic mechanisms, including DNA methylation, histone modifications and non-coding RNA, are a proposed link between environmental stressors, alterations in gene expression, and phenotypes. Epigenetic modifications play a primary role in shaping functional differences between cell types and can be modified by environmental perturbations, especially in early development. Together with contributions from genetic variation, epigenetic mechanisms orchestrate patterns of gene expression within specific cell types that contribute to phenotypic variation between individuals. To date, many studies have provided insights into epigenetic changes resulting from ELS. However, most of these studies have examined heterogenous brain tissue, despite evidence of cell-type-specific epigenetic modifications in phenotypes associated with ELS. In this review, we focus on rodent and human studies that have examined epigenetic modifications induced by ELS in select cell types isolated from the brain or associated with genes that have cell-type-restricted expression in neurons, microglia, astrocytes, and oligodendrocytes. Although significant challenges remain, future studies using these approaches can enable important mechanistic insight into the role of epigenetic variation in the effects of ELS on brain function.
Molecular characterization of the missing electron pathways for butanol synthesis in Clostridium acetobutylicum
Authors: Foulquier Céline , Rivière Antoine , Heulot Mathieu , Dos Reis Suzanna , Perdu Caroline , Girbal Laurence , Pinault Mailys , Dusséaux Simon , Yoo Minyeong , Soucaille Philippe , Meynial-Salles Isabelle 
Published: August 2022

AbstractClostridium acetobutylicum is a promising biocatalyst for the renewable production of n-butanol. Several metabolic strategies have already been developed to increase butanol yields, most often based on carbon pathway redirection. However, it has previously demonstrated that the activities of both ferredoxin-NADP+ reductase and ferredoxin-NAD+ reductase, whose encoding genes remain unknown, are necessary to produce the NADPH and the extra NADH needed for butanol synthesis under solventogenic conditions. Here, we purify, identify and partially characterize the proteins responsible for both activities and demonstrate the involvement of the identified enzymes in butanol synthesis through a reverse genetic approach. We further demonstrate the yield of butanol formation is limited by the level of expression of CA_C0764, the ferredoxin-NADP+ reductase encoding gene and the bcd operon, encoding a ferredoxin-NAD+ reductase. The integration of these enzymes into metabolic engineering strategies introduces opportunities for developing a homobutanologenic C. acetobutylicum strain.
Evidence for a HURP/EB free mixed-nucleotide zone in kinetochore-microtubules
Authors: Castrogiovanni Cédric , Inchingolo Alessio V. , Harrison Jonathan U. , Dudka Damian , Sen Onur , Burroughs Nigel J. , McAinsh Andrew D. , Meraldi Patrick 
Published: August 2022

AbstractCurrent models infer that the microtubule-based mitotic spindle is built from GDP-tubulin with small GTP caps at microtubule plus-ends, including those that attach to kinetochores, forming the kinetochore-fibres. Here we reveal that kinetochore-fibres additionally contain a dynamic mixed-nucleotide zone that reaches several microns in length. This zone becomes visible in cells expressing fluorescently labelled end-binding proteins, a known marker for GTP-tubulin, and endogenously-labelled HURP - a protein which we show to preferentially bind the GDP microtubule lattice in vitro and in vivo. We find that in mitotic cells HURP accumulates on the kinetochore-proximal region of depolymerising kinetochore-fibres, whilst avoiding recruitment to nascent polymerising K-fibres, giving rise to a growing “HURP-gap”. The absence of end-binding proteins in the HURP-gaps leads us to postulate that they reflect a mixed-nucleotide zone. We generate a minimal quantitative model based on the preferential binding of HURP to GDP-tubulin to show that such a mixed-nucleotide zone is sufficient to recapitulate the observed in vivo dynamics of HURP-gaps.
mTORC1 controls Golgi architecture and vesicle secretion by phosphorylation of SCYL1
Authors: Kaeser-Pebernard Stéphanie , Vionnet Christine , Mari Muriel , Sankar Devanarayanan Siva , Hu Zehan , Roubaty Carole , Martínez-Martínez Esther , Zhao Huiyuan , Spuch-Calvar Miguel , Petri-Fink Alke , Rainer Gregor , Steinberg Florian , Reggiori Fulvio , Dengjel Jörn 
Published: August 2022

AbstractThe protein kinase mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of cell growth and proliferation, supporting anabolic reactions and inhibiting catabolic pathways like autophagy. Its hyperactivation is a frequent event in cancer promoting tumor cell proliferation. Several intracellular membrane-associated mTORC1 pools have been identified, linking its function to distinct subcellular localizations. Here, we characterize the N-terminal kinase-like protein SCYL1 as a Golgi-localized target through which mTORC1 controls organelle distribution and extracellular vesicle secretion in breast cancer cells. Under growth conditions, SCYL1 is phosphorylated by mTORC1 on Ser754, supporting Golgi localization. Upon mTORC1 inhibition, Ser754 dephosphorylation leads to SCYL1 displacement to endosomes. Peripheral, dephosphorylated SCYL1 causes Golgi enlargement, redistribution of early and late endosomes and increased extracellular vesicle release. Thus, the mTORC1-controlled phosphorylation status of SCYL1 is an important determinant regulating subcellular distribution and function of endolysosomal compartments. It may also explain the pathophysiology underlying human genetic diseases such as CALFAN syndrome, which is caused by loss-of-function of SCYL1.
Determination of the asymptotic limits of adaptive photon counting measurements for coherent-state optical phase estimation
Authors: Rodríguez-García M. A. , DiMario M. T. , Barberis-Blostein P. , Becerra F. E. 
Published: August 2022

AbstractPhysical realizations of the canonical phase measurement for the optical phase are unknown. Single-shot phase estimation, which aims to determine the phase of an optical field in a single shot, is critical in quantum information processing and metrology. Here we present a family of strategies for single-shot phase estimation of coherent states based on adaptive non-Gaussian, photon counting, measurements with coherent displacements that maximize information gain as the measurement progresses, which have higher sensitivities over the best known adaptive Gaussian strategies. To gain understanding about their fundamental characteristics and demonstrate their superior performance, we develop a comprehensive statistical analysis based on Bayesian optimal design of experiments, which provides a natural description of these non-Gaussian strategies. This mathematical framework, together with numerical analysis and Monte Carlo methods, allows us to determine the asymptotic limits in sensitivity of strategies based on photon counting designed to maximize information gain, which up to now had been a challenging problem. Moreover, we show that these non-Gaussian phase estimation strategies have the same functional form as the canonical phase measurement in the asymptotic limit differing only by a scaling factor, thus providing the highest sensitivity among physically-realizable measurements for single-shot phase estimation of coherent states known to date. This work shines light into the potential of optimized non-Gaussian measurements based on photon counting for optical quantum metrology and phase estimation.
Towards understanding the magnetic properties of the breathing pyrochlore compound Ba3Yb2Zn5O11through single-crystal studies
Authors: Dissanayake Sachith , Shi Zhenzhong , Rau Jeffrey G. , Bag Rabindranath , Steinhardt William , Butch Nicholas P. , Frontzek Matthias , Podlesnyak Andrey , Graf David , Marjerrison Casey , Liu Jue , Gingras Michel J. P. , Haravifard Sara 
Published: August 2022

AbstractBa3Yb2Zn5O11 is exceptional among breathing pyrochlore compounds for being in the nearly-decoupled limit where inter-tetrahedron interactions are weak, hosting isolated clusters or molecular magnet-like tetrahedra of magnetic ytterbium (Yb3+) ions. In this work, we present the study carried out on single-crystal samples of the breathing pyrochlore Ba3Yb2Zn5O11, using a variety of magnetometry and neutron scattering techniques along with theoretical modeling. We employ inelastic neutron scattering to investigate the magnetic dynamics as a function of applied field (with respect to both magnitude and direction) down to a temperature of 70 mK, where inelastic scattering reveals dispersionless bands of excitations as found in earlier powder sample studies, in good agreement with a single-tetrahedron model. However, diffuse neutron scattering at zero field and dc-susceptibility at finite field exhibit features suggesting the presence of excitations at low-energy that are not captured by the single tetrahedron model. Analysis of the local structure down to 2 K via pair distribution function analysis finds no evidence of structural disorder. We conclude that effects beyond the single tetrahedron model are important in describing the low-energy, low-temperature physics of Ba3Yb2Zn5O11, but their nature remains undetermined.
The effects of the voglibose on non-alcoholic fatty liver disease in mice model
Authors: Bae Jaehyun , Lee Ji Young , Shin Eugene , Lee Minyoung , Lee Yong-ho , Lee Byung-Wan , Kang Eun Seok , Cha Bong-Soo 
Published: August 2022

AbstractThe α-glucosidase inhibitor (α-GI) delays the intestinal absorption of glucose, which reduces postprandial hepatic glucose intake. This mechanism is considered to be effective in treating non-alcoholic fatty liver disease (NAFLD). Here, we investigated the effect of voglibose, an α-glucosidase inhibitor, on high-fat, high-fructose (HFHFr) diet-induced NAFLD models. Seven-week-old male C57BL/6J mice were randomly placed in a chow diet group or an HFHFr diet group. After 10 weeks, mice in the HFHFr group were randomly assigned to one of three groups: HFHFr diet with vehicle, HFHFr with voglibose, or HFHFr with pioglitazone. Each diet and treatment was continued for 10 weeks. The HFHFr diet induced severe NAFLD in terms of steatosis, hepatitis, and fibrosis. Administration of voglibose improved all aspects of NAFLD, comparable to those of pioglitazone, a positive control. In voglibose-treated mice, gene expressions of hepatic lipogenesis markers were significantly downregulated. In the in vitro experiment, reducing the influx of glucose into hepatocytes significantly reduced steatosis and de novo lipogenesis even in the presence of sufficient fructose and fat, demonstrating that the mechanism of voglibose could be effective in treating HFHFr diet-induced NAFLD. These results indicate that voglibose improves HFHFr diet-induced NAFLD by suppressing hepatic de novo lipogenesis.
Experimental study on compression mechanical characteristics of filled rock joints after multiple pre-impacts
Authors: Chai Shaobo , Jia Yongsheng , Du Yuxiang , Hu Bo , Li Xianpeng 
Published: August 2022

AbstractThe prefabricated artificial filled jointed rock specimens are impacted by a self-made drop hammer impact device for many times, and the specimens with different degrees of cumulative damage characteristics are obtained. Then, the static and dynamic compression mechanical properties are studied by using universal testing machine and SHPB device. Through the static compression test, the strength and deformation characteristics of jointed rock specimens after multiple impacts are obtained, and the influence of the damage degree of jointed rock specimens characterized by wave velocity on the compressive strength of filled joints is analysed. Based on the results of SHPB impact test, the dynamic strength and deformation evolution, wave propagation law and energy dissipation law of filled joints after multiple impacts are analysed. During the SHPB test, the impact failure process of rock specimens is recorded by a high-speed camera. The experimental results show that the damage degree of jointed rock samples increases nonlinearly after multiple impacts. The attenuation laws of static strength and dynamic strength of rock samples under the same damage evolution conditions are different. With the increase of impact times, the failure mode of jointed rock samples after damage is simpler and tends to compression failure.
Exploring the brachistochrone (shortest-time) path in fire spread
Authors: Sun Peiyi , Liu Yanhui , Huang Xinyan 
Published: August 2022

AbstractThe brachistochrone (shortest-time) curve is the path connecting two points that enables the shortest travel time. This work explores the “brachistochrone path” of fire spread connecting two points at the same altitude and with a fixed path length. The starting and ending points are connected by both thermally thin fuels (thin wires) and thermally thick fuels (PMMA bars). Flame-spread paths of triangular, rectangular, and circular shapes with different heights and inclinations are explored. Results show that having a local maximum flame-spread rate does not result in the shortest overall travel time. For thin-wire paths, the fastest overall-path fire spread occurs, when the upward spread path is vertical, and the path height reaches a maximum, as demonstrated by the theoretical analysis. Differently, for thick PMMA-bar paths, the brachistochrone condition occurs when the path length of the vertical upward spread reaches the maximum, because the upward spread is about ten times faster than the downward spread. This study extends the conventional problem of the fastest fire spread to the shortest-time problem of the whole fire path, and it may help optimize the fuel distribution inside the built environment and estimate available safe egress time in building and wildland fires.
Absolute binding free energy calculations improve enrichment of actives in virtual compound screening
Authors: Feng Mudong , Heinzelmann Germano , Gilson Michael K. 
Published: August 2022

AbstractWe determined the effectiveness of absolute binding free energy (ABFE) calculations to refine the selection of active compounds in virtual compound screening, a setting where the more commonly used relative binding free energy approach is not readily applicable. To do this, we conducted baseline docking calculations of structurally diverse compounds in the DUD-E database for three targets, BACE1, CDK2 and thrombin, followed by ABFE calculations for compounds with high docking scores. The docking calculations alone achieved solid enrichment of active compounds over decoys. Encouragingly, the ABFE calculations then improved on this baseline. Analysis of the results emphasizes the importance of establishing high quality ligand poses as starting points for ABFE calculations, a nontrivial goal when processing a library of diverse compounds without informative co-crystal structures. Overall, our results suggest that ABFE calculations can play a valuable role in the drug discovery process.
Validation of droplet digital PCR for cytokeratin 19 mRNA detection in canine peripheral blood and mammary gland
Authors: Tanvetthayanont Potsawat , Yata Teerapong , Boonnil Jiranun , Temisak Sasithon , Ponglowhapan Suppawiwat 
Published: August 2022

AbstractIn humans, peripheral blood cytokeratin 19 (CK19) mRNA-positive circulating tumor cells (CTCs) was utilized to identify early-stage breast cancer patients with micrometastatic disease who are at risk for disease progression and monitor treatment response in patients with advanced disease. To our knowledge, there has been little research regarding CK19 in canine mammary tumors (CMTs) using molecular methods. A droplet digital PCR (ddPCR) is proposed as a precise and sensitive quantification of nucleic acid targets. Hence, this study aimed to validate a newly designed assay for CK19 detection in canine blood and mammary tissue, along with the reference gene HPRT, by ddPCR. All primers and probes showed a precise match with the exon region of target genes. The assay exhibited PCR efficacy of 90.4% and 91.0% for CK19 and HPRT amplifications with linearity, respectively. The annealing temperature (Ta) for duplex ddPCR was 55 °C, providing the highest concentrations of both genes tested by the synthetic plasmid DNA. The limit of detection (LOD) of CK19 and HPRT were 2.16 ± 1.27 and 2.44 ± 1.31 copies/µL, respectively. Finally, the ddPCR assay was validated with canine peripheral blood, non-neoplastic mammary tissues and spiked samples. Our findings provide a new platform for CK19 studies in CMT diagnosis through blood and mammary tissues.
Neoadjuvant chemotherapy or upfront surgery in localized pancreatic cancer: a contemporary analysis
Authors: Uson Junior Pedro Luiz Serrano , Carvalho Leonardo , Fernandes Milena Lourenço Coleta , Botrus Gehan , de Souza Martins Rodrigo , da Silva Elaine Ferreira , dos Santos Sarah Silva Mello Batista , Taniwaki Leticia , Taranto Patrícia , Dutra Ana Carolina Pereira , de Oliveira Filho João Bosco , Araujo Sergio Eduardo Alonso , Moura Fernando 
Published: August 2022

AbstractNeoadjuvant chemotherapy is considered a new treatment option for potentially resectable pancreatic cancer. However, data are not well established on overall survival and delaying surgery in resectable pancreatic cancer, as well as on those patients that ultimately cannot undergo surgery. We analyzed pancreatic cancer patients treated in a tertiary hospital from January 2016 to December 2020. Patients with resectable stage I and II pancreatic cancer were evaluated regarding surgery, neoadjuvant treatment, and other clinical demographics. The survival function was estimated using the Kaplan–Meier method, and the relationship between the variables of interest and the overall survival (OS) was assessed by adopting the proportional regression Cox models. A total of 216 patients were evaluated. 81 of them with resectable/borderline resectable disease and 135 with unresectable /metastatic disease at diagnosis. Median OS for stage I and II disease were 36 and 28 months, respectively. For resectable pancreatic cancer median OS was 28 months, for borderline resectable pancreatic cancer median OS was 11 months. Median OS for stage III (locally advanced) and stage IV (metastatic) were 10 and 7 months, respectively (p < 0.0001). Median OS of 9 months were obtained for patients with stage I and II that did not undergo surgery compared to 25 months in patients that underwent surgery in any time (p < 0.001). Comparing patients with localized disease, median OS for patients treated with upfront surgery was 28 months, compared to 15 months in patients treated with neoadjuvant approach (p = 0.04). Most patients that did not undergo surgery have decline of performance status or disease progression on neoadjuvant treatment. On multivariable analysis in pancreatic cancer stages I and II, including age, sex, borderline or resectable disease, CA 19–9, positive lymph nodes and neoadjuvant treatment, the surgery was the only factor associated with improved overall survival (p = 0.04). Upfront surgery should still be considered a standard of care approach for resectable pancreatic cancer. Biomarker driven studies and randomized trials with combination therapies are necessary to address neoadjuvant chemotherapy and delaying surgery in purely resectable pancreatic cancer.
Spin revolution breaks time reversal symmetry of rolling magnets
Authors: Vedmedenko Elena Y. , Wiesendanger Roland 
Published: August 2022

AbstractThe classical laws of physics are usually invariant under time reversal. Here, we reveal a novel class of magnetomechanical effects rigorously breaking time-reversal symmetry. These effects are based on the mechanical rotation of a hard magnet around its magnetization axis in the presence of friction and an external magnetic field, which we call spin revolution. The spin revolution leads to a variety of symmetry breaking phenomena including upward propulsion on vertical surfaces defying gravity as well as magnetic gyroscopic motion that is perpendicular to the applied force. The angular momentum of spin revolution differs from those of the magnetic field, the magnetic torque, the rolling axis, and the net torque about the rolling axis. The spin revolution emerges spontaneously, without external rotations, and offers various applications in areas such as magnetism, robotics and energy harvesting.
Transcriptional dynamics of colorectal cancer risk associated variation at 11q23.1 correlate with tuft cell abundance and marker expression in silico
Authors: Harris Bradley T. , Rajasekaran Vidya , Blackmur James P. , O’Callaghan Alan , Donnelly Kevin , Timofeeva Maria , Vaughan-Shaw Peter G. , Din Farhat V. N. , Dunlop Malcolm G. , Farrington Susan M. 
Published: August 2022

AbstractColorectal cancer (CRC) is characterised by heritable risk that is not well understood. Heritable, genetic variation at 11q23.1 is associated with increased colorectal cancer (CRC) risk, demonstrating eQTL effects on 3 cis- and 23 trans-eQTL targets. We sought to determine the relationship between 11q23.1 cis- and trans-eQTL target expression and test for potential cell-specificity. scRNAseq from 32,361 healthy colonic epithelial cells was aggregated and subject to weighted gene co-expression network analysis (WGCNA). One module (blue) included 19 trans-eQTL targets and was correlated withPOU2AF2expression only. Following unsupervised clustering of single cells, the expression of 19 trans-eQTL targets was greatest and most variable in cluster number 11, which transcriptionally resembled tuft cells. 14 trans-eQTL targets were found to demarcate this cluster, 11 of which were corroborated in a second dataset. Intra-cluster WGCNA and module preservation analysis then identified twelve 11q23.1 trans-eQTL targets to comprise a network that was specific to cluster 11. Finally, linear modelling and differential abundance testing showed 11q23.1 trans-eQTL target expression was predictive of cluster 11 abundance. Our findings suggest 11q23.1 trans-eQTL targets comprise aPOU2AF2-related network that is likely tuft cell-specific and reduced expression of these genes correlates with reduced tuft cell abundance in silico.