bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chromatin accessibility associates with protein-RNA correlation in human cancer
Authors: Sanghi Akshay , Gruber Joshua J. , Metwally Ahmed , Jiang Lihua , Reynolds Warren , Sunwoo John , Orloff Lisa , Chang Howard Y. , Kasowski Maya , Snyder Michael P. 
Published: September 2021

AbstractAlthough alterations in chromatin structure are known to exist in tumors, how these alterations relate to molecular phenotypes in cancer remains to be demonstrated. Multi-omics profiling of human tumors can provide insight into how alterations in chromatin structure are propagated through the pathway of gene expression to result in malignant protein expression. We applied multi-omics profiling of chromatin accessibility, RNA abundance, and protein abundance to 36 human thyroid cancer primary tumors, metastases, and patient-match normal tissue. Through quantification of chromatin accessibility associated with active transcription units and global protein expression, we identify a local chromatin structure that is highly correlated with coordinated RNA and protein expression. In particular, we identify enhancers located within gene-bodies as predictive of correlated RNA and protein expression, that is independent of overall transcriptional activity. To demonstrate the generalizability of these findings we also identify similar results in an independent cohort of human breast cancers. Taken together, these analyses suggest that local enhancers, rather than distal enhancers, are likely most predictive of cancer gene expression phenotypes. This allows for identification of potential targets for cancer therapeutic approaches and reinforces the utility of multi-omics profiling as a methodology to understand human disease.
High-level cognition during story listening is reflected in high-order dynamic correlations in neural activity patterns
Authors: Owen Lucy L. W. , Chang Thomas H. , Manning Jeremy R. 
Published: September 2021

AbstractOur thoughts arise from coordinated patterns of interactions between brain structures that change with our ongoing experiences. High-order dynamic correlations in neural activity patterns reflect different subgraphs of the brain’s functional connectome that display homologous lower-level dynamic correlations. Here we test the hypothesis that high-level cognition is reflected in high-order dynamic correlations in brain activity patterns. We develop an approach to estimating high-order dynamic correlations in timeseries data, and we apply the approach to neuroimaging data collected as human participants either listen to a ten-minute story or listen to a temporally scrambled version of the story. We train across-participant pattern classifiers to decode (in held-out data) when in the session each neural activity snapshot was collected. We find that classifiers trained to decode from high-order dynamic correlations yield the best performance on data collected as participants listened to the (unscrambled) story. By contrast, classifiers trained to decode data from scrambled versions of the story yielded the best performance when they were trained using first-order dynamic correlations or non-correlational activity patterns. We suggest that as our thoughts become more complex, they are reflected in higher-order patterns of dynamic network interactions throughout the brain.
Time-varying data processing with nonvolatile memristor-based temporal kernel
Authors: Jang Yoon Ho , Kim Woohyun , Kim Jihun , Woo Kyung Seok , Lee Hyun Jae , Jeon Jeong Woo , Shim Sung Keun , Han Janguk , Hwang Cheol Seong 
Published: September 2021

Abstract
Recent advances in physical reservoir computing, which is a type of temporal kernel, have made it possible to perform complicated timing-related tasks using a linear classifier. However, the fixed reservoir dynamics in previous studies have limited application fields. In this study, temporal kernel computing was implemented with a physical kernel that consisted of a W/HfO2/TiN memristor, a capacitor, and a resistor, in which the kernel dynamics could be arbitrarily controlled by changing the circuit parameters. After the capability of the temporal kernel to identify the static MNIST data was proven, the system was adopted to recognize the sequential data, ultrasound (malignancy of lesions) and electrocardiogram (arrhythmia), that had a significantly different time constant (10−7 vs. 1 s). The suggested system feasibly performed the tasks by simply varying the capacitance and resistance. These functionalities demonstrate the high adaptability of the present temporal kernel compared to the previous ones.
Elucidating gene expression adaptation of phylogenetically divergent coral holobionts under heat stress
Authors: Avila-Magaña Viridiana , Kamel Bishoy , DeSalvo Michael , Gómez-Campo Kelly , Enríquez Susana , Kitano Hiroaki , Rohlfs Rori V. , Iglesias-Prieto Roberto , Medina Mónica 
Published: September 2021

AbstractAs coral reefs struggle to survive under climate change, it is crucial to know whether they have the capacity to withstand changing conditions, particularly increasing seawater temperatures. Thermal tolerance requires the integrative response of the different components of the coral holobiont (coral host, algal photosymbiont, and associated microbiome). Here, using a controlled thermal stress experiment across three divergent Caribbean coral species, we attempt to dissect holobiont member metatranscriptome responses from coral taxa with different sensitivities to heat stress and use phylogenetic ANOVA to study the evolution of gene expression adaptation. We show that coral response to heat stress is a complex trait derived from multiple interactions among holobiont members. We identify host and photosymbiont genes that exhibit lineage-specific expression level adaptation and uncover potential roles for bacterial associates in supplementing the metabolic needs of the coral-photosymbiont duo during heat stress. Our results stress the importance of integrative and comparative approaches across a wide range of species to better understand coral survival under the predicted rise in sea surface temperatures.
NG2 glia-derived GABA release tunes inhibitory synapses and contributes to stress-induced anxiety
Authors: Zhang Xiao , Liu Yao , Hong Xiaoqi , Li Xia , Meshul Charles K. , Moore Cynthia , Yang Yabing , Han Yanfei , Li Wei-Guang , Qi Xin , Lou Huifang , Duan Shumin , Xu Tian-Le , Tong Xiaoping 
Published: September 2021

AbstractNG2 glia, also known as oligodendrocyte precursor cells (OPCs), play an important role in proliferation and give rise to myelinating oligodendrocytes during early brain development. In contrast to other glial cell types, the most intriguing aspect of NG2 glia is their ability to directly sense synaptic inputs from neurons. However, whether this synaptic interaction is bidirectional or unidirectional, or its physiological relevance has not yet been clarified. Here, we report that NG2 glia form synaptic complexes with hippocampal interneurons and that selective photostimulation of NG2 glia (expressing channelrhodopsin-2) functionally drives GABA release and enhances inhibitory synaptic transmission onto proximal interneurons in a microcircuit. The mechanism involves GAD67 biosynthesis and VAMP-2 containing vesicular exocytosis. Further, behavioral assays demonstrate that NG2 glia photoactivation triggers anxiety-like behavior in vivo and contributes to chronic social defeat stress.
Environmental eustress modulates β-ARs/CCL2 axis to induce anti-tumor immunity and sensitize immunotherapy against liver cancer in mice
Authors: Liu Chaobao , Yang Yang , Chen Cheng , Li Ling , Li Jingquan , Wang Xiaonan , Chu Qiao , Qiu Lin , Ba Qian , Li Xiaoguang , Wang Hui 
Published: September 2021

AbstractAlthough psycho-social stress is a well-known factor that contributes to the development of cancer, it remains largely unclear whether and how environmental eustress influences malignant diseases and regulates cancer-related therapeutic responses. Using an established eustress model, we demonstrate that mice living in an enriched environment (EE) are protected from carcinogen-induced liver neoplasia and transplantable syngeneic liver tumors, owning to a CD8+ T cell-dependent tumor control. We identify a peripheral Neuro-Endocrine-Immune pathway in eustress, including Sympathetic nervous system (SNS)/β-adrenergic receptors (β-ARs)/CCL2 that relieves tumor immunosuppression and overcomes PD-L1 resistance to immunotherapy. Notably, EE activates peripheral SNS and β-ARs signaling in tumor cells and tumor infiltrated myeloid cells, leading to suppression of CCL2 expression and activation of anti-tumor immunity. Either blockade of CCL2/CCR2 or β-AR signaling in EE mice lose the tumor protection capability. Our study reveales that environmental eustress via EE stimulates anti-tumor immunity, resulting in more efficient tumor control and a better outcome of immunotherapy.
Substrate colonization by an emulsion drop prior to spreading
Authors: Borkar Suraj , Ramachandran Arun 
Published: September 2021

AbstractIn classical wetting, the spreading of an emulsion drop on a surface is preceded by the formation of a bridge connecting the drop and the surface across the sandwiched film of the suspending medium. However, this widely accepted mechanism ignores the finite solubility of the drop phase in the medium. We present experimental evidence of a new wetting mechanism, whereby the drop dissolves in the medium, and nucleates on the surface as islands that grow with time. Island growth is predicated upon a reduction in solubility near the contact line due to attractive interactions between the drop and the surface, overcoming Ostwald ripening. Ultimately, wetting is manifested as a coalescence event between the parent drop and one of the islands, which can result in significantly large critical film heights and short hydrodynamic drainage times prior to wetting. This discovery has broad relevance in areas such as froth flotation, liquid-infused surfaces, multiphase flows and microfluidics.
Cell membrane coating integrity affects the internalization mechanism of biomimetic nanoparticles
Authors: Liu Lizhi , Bai Xuan , Martikainen Maria-Viola , Kårlund Anna , Roponen Marjut , Xu Wujun , Hu Guoqing , Tasciotti Ennio , Lehto Vesa-Pekka 
Published: September 2021

AbstractCell membrane coated nanoparticles (NPs) have recently been recognized as attractive nanomedical tools because of their unique properties such as immune escape, long blood circulation time, specific molecular recognition and cell targeting. However, the integrity of the cell membrane coating on NPs, a key metrics related to the quality of these biomimetic-systems and their resulting biomedical function, has remained largely unexplored. Here, we report a fluorescence quenching assay to probe the integrity of cell membrane coating. In contradiction to the common assumption of perfect coating, we uncover that up to 90% of the biomimetic NPs are only partially coated. Using in vitro homologous targeting studies, we demonstrate that partially coated NPs could still be internalized by the target cells. By combining molecular simulations with experimental analysis, we further identify an endocytic entry mechanism for these NPs. We unravel that NPs with a high coating degree (≥50%) enter the cells individually, whereas the NPs with a low coating degree (<50%) need to aggregate together before internalization. This quantitative method and the fundamental understanding of how cell membrane coated NPs enter the cells will enhance the rational designing of biomimetic nanosystems and pave the way for more effective cancer nanomedicine.
Efficient CO2 electroreduction on facet-selective copper films with high conversion rate
Authors: Zhang Gong , Zhao Zhi-Jian , Cheng Dongfang , Li Huimin , Yu Jia , Wang Qingzhen , Gao Hui , Guo Jinyu , Wang Huaiyuan , Ozin Geoffrey A. , Wang Tuo , Gong Jinlong 
Published: September 2021

AbstractTuning the facet exposure of Cu could promote the multi-carbon (C2+) products formation in electrocatalytic CO2 reduction. Here we report the design and realization of a dynamic deposition-etch-bombardment method for Cu(100) facets control without using capping agents and polymer binders. The synthesized Cu(100)-rich films lead to a high Faradaic efficiency of 86.5% and a full-cell electricity conversion efficiency of 36.5% towards C2+ products in a flow cell. By further scaling up the electrode into a 25 cm2 membrane electrode assembly system, the overall current can ramp up to 12 A while achieving a single-pass yield of 13.2% for C2+ products. An insight into the influence of Cu facets exposure on intermediates is provided by in situ spectroscopic methods supported by theoretical calculations. The collected information will enable the precise design of CO2 reduction reactions to obtain desired products, a step towards future industrial CO2 refineries.
A complex of BRCA2 and PP2A-B56 is required for DNA repair by homologous recombination
Authors: Ambjørn Sara M. , Duxin Julien P. , Hertz Emil P. T. , Nasa Isha , Duro Joana , Kruse Thomas , Lopez-Mendez Blanca , Rymarczyk Beata , Cressey Lauren E. , van Overeem Hansen Thomas , Kettenbach Arminja N. , Oestergaard Vibe H. , Lisby Michael , Nilsson Jakob 
Published: September 2021

AbstractMutations in the tumour suppressor gene BRCA2 are associated with predisposition to breast and ovarian cancers. BRCA2 has a central role in maintaining genome integrity by facilitating the repair of toxic DNA double-strand breaks (DSBs) by homologous recombination (HR). BRCA2 acts by controlling RAD51 nucleoprotein filament formation on resected single-stranded DNA, but how BRCA2 activity is regulated during HR is not fully understood. Here, we delineate a pathway where ATM and ATR kinases phosphorylate a highly conserved region in BRCA2 in response to DSBs. These phosphorylations stimulate the binding of the protein phosphatase PP2A-B56 to BRCA2 through a conserved binding motif. We show that the phosphorylation-dependent formation of the BRCA2-PP2A-B56 complex is required for efficient RAD51 filament formation at sites of DNA damage and HR-mediated DNA repair. Moreover, we find that several cancer-associated mutations in BRCA2 deregulate the BRCA2-PP2A-B56 interaction and sensitize cells to PARP inhibition. Collectively, our work uncovers PP2A-B56 as a positive regulator of BRCA2 function in HR with clinical implications for BRCA2 and PP2A-B56 mutated cancers.
Preclinical development of a bispecific TNFα/IL-23 neutralising domain antibody as a novel oral treatment for inflammatory bowel disease
Authors: Roberts Kevin J. , Cubitt Marion F. , Carlton Timothy M. , Rodrigues-Duarte Lurdes , Maggiore Luana , Chai Ray , Clare Simon , Harcourt Katherine , MacDonald Thomas T. , Ray Keith P. , Vossenkämper Anna , West Michael R. , Crowe J. Scott 
Published: September 2021

AbstractAnti-TNFα and anti-IL-23 antibodies are highly effective therapies for Crohn’s disease or ulcerative colitis in a proportion of patients. V56B2 is a novel bispecific domain antibody in which a llama-derived IL-23p19-specific domain antibody, humanised and engineered for intestinal protease resistance, V900, was combined with a previously-described TNFα-specific domain antibody, V565. V56B2 contains a central protease-labile linker to create a single molecule for oral administration. Incubation of V56B2 with trypsin or human faecal supernatant resulted in a complete separation of the V565 and V900 monomers without loss of neutralising potency. Following oral administration of V900 and V565 in mice, high levels of each domain antibody were detected in the faeces, demonstrating stability in the intestinal milieu. In ex vivo cultures of colonic biopsies from IBD patients, treatment with V565 or V900 inhibited tissue phosphoprotein levels and with a combination of the two, inhibition was even greater. These results support further development of V56B2 as an oral therapy for IBD with improved safety and efficacy in a greater proportion of patients as well as greater convenience for patients compared with traditional monoclonal antibody therapies.
The virucidal effects of 405 nm visible light on SARS-CoV-2 and influenza A virus
Authors: Rathnasinghe Raveen , Jangra Sonia , Miorin Lisa , Schotsaert Michael , Yahnke Clifford , Garcίa-Sastre Adolfo 
Published: September 2021

AbstractThe germicidal potential of specific wavelengths within the electromagnetic spectrum is an area of growing interest. While ultra-violet (UV) based technologies have shown satisfactory virucidal potential, the photo-toxicity in humans coupled with UV associated polymer degradation limit their use in occupied spaces. Alternatively, longer wavelengths with less irradiation energy such as visible light (405 nm) have largely been explored in the context of bactericidal and fungicidal applications. Such studies indicated that 405 nm mediated inactivation is caused by the absorbance of porphyrins within the organism creating reactive oxygen species which result in free radical damage to its DNA and disruption of cellular functions. The virucidal potential of visible-light based technologies has been largely unexplored and speculated to be ineffective given the lack of porphyrins in viruses. The current study demonstrated increased susceptibility of lipid-enveloped respiratory pathogens of importance such as SARS-CoV-2 (causative agent of COVID-19) and influenza A virus to 405 nm, visible light in the absence of exogenous photosensitizers thereby indicating a potential alternative porphyrin-independent mechanism of visible light mediated viral inactivation. These results were obtained using less than expected irradiance levels which are considered safe for humans and commercially achievable. Our results support further exploration of the use of visible light technology for the application of continuous decontamination in occupied areas within hospitals and/or infectious disease laboratories, specifically for the inactivation of respiratory pathogens such as SARS-CoV-2 and Influenza A.
Dental replacement in Mesozoic birds: evidence from newly discovered Brazilian enantiornithines
Authors: Wu Yun-Hsin , Chiappe Luis M. , Bottjer David J. , Nava William , Martinelli Agustín G. 
Published: September 2021

AbstractPolyphyodonty—multiple tooth generations—in Mesozoic birds has been confirmed since the nineteenth century. Their dental cycle had been assessed through sparse data from tooth roots revealed through broken jawbones and disattached teeth. However, detailed descriptions of their tooth cycling are lacking, and the specifics of their replacement patterns remain largely unknown. Here we present unprecedented µCT data from three enantiornithine specimens from the Upper Cretaceous of southeastern Brazil. The high resolution µCT data show an alternating dental replacement pattern in the premaxillae, consistent with the widespread pattern amongst extinct and extant reptiles. The dentary also reveals dental replacement at different stages. These results strongly suggest that an alternating pattern was typical of enantiornithine birds. µCT data show that new teeth start lingually within the alveoli, resorb roots of functional teeth and migrate labially into their pulp cavities at an early stage, similar to modern crocodilians. Our results imply that the control mechanism for tooth cycling is conserved during the transition between non-avian reptiles and birds. These first 3D reconstructions of enantiornithine dental replacement demonstrate that 3D data are essential to understand the evolution and deep homology of archosaurian tooth cycling.
Adverse outcomes after noncardiac surgery in patients with aortic stenosis
Authors: Tai Ying-Hsuan , Chang Chuen-Chau , Yeh Chun-Chieh , Cherng Yih-Giun , Chen Ta-Liang , Liao Chien-Chang 
Published: September 2021

AbstractWhether aortic stenosis (AS) increases perioperative risk in noncardiac surgery remains controversial. Limited information is available regarding adequate anesthetic techniques for patients with AS. Using the reimbursement claims data of Taiwan’s National Health Insurance, we performed propensity score matching analyses to evaluate the risk of adverse outcomes in patients with or without AS undergoing noncardiac surgery between 2008 and 2013. We also compared the perioperative risk of AS patients undergoing general anesthesia or neuraxial anesthesia. Multivariable logistic regressions were applied to calculate the adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for postoperative mortality and major complications. The matching procedure generated 9741 matched pairs for analyses. AS was significantly associated with 30-day in-hospital mortality (aOR 1.31, 95% CI 1.03–1.67), acute renal failure (aOR 1.42, 95% CI 1.12–1.79), pneumonia (aOR 1.16, 95% CI 1.02–1.33), stroke (aOR 1.14, 95% CI 1.01–1.29), and intensive care unit stay (aOR 1.38, 95% CI 1.27–1.49). Compared with neuraxial anesthesia, general anesthesia was associated with increased risks of acute myocardial infarction (aOR 3.06, 95% CI 1.22–7.67), pneumonia (aOR 1.80, 95% CI 1.32–2.46), acute renal failure (aOR 1.82, 95% CI 1.11–2.98), and intensive care (aOR 4.05, 95% CI 3.23–5.09). The findings were generally consistent across subgroups. AS was an independent risk factor for adverse events after noncardiac surgery. In addition, general anesthesia was associated with greater postoperative complications in AS patients compared to neuraxial anesthesia. This real-world evidence suggests that neuraxial anesthesia should not be contraindicated in patients with AS.
Effect of functional oils or probiotics on performance and microbiota profile of newly weaned piglets
Authors: Vieira Alexandre Maciel , Sessin Amanda Pires , Soratto Tatiany Aparecida Teixeira , Pires Paula Gabriela da Silva , Cardinal Kátia Maria , Wagner Glauber , Hauptli Lucélia , Lima André Luis Ferreira , Dahlke Fabiano , Netto Diego Peres , Moraes Priscila de Oliveira 
Published: September 2021

AbstractThe study aimed to evaluate a commercial blend of functional oils based on liquid from the cashew nutshell and castor oil as a growth promoter in newly weaned piglets. A total of 225 piglets, castrated males and females with 28 days of age were randomly distributed in pens with 15 animals composing three treatments and five repetitions. The treatments were: control (without the inclusion of additives), probiotics, or functional oils. The performance was evaluated. At 50 days of age, a pool of fresh feces from 3 animals/repetition was collected to perform the sequencing of microbiota using the Illumina MiSeq platform. Supplementation with functional oils improved the piglets' daily weight gain and feed conversion ratio (P < 0.05) in the first weeks of the experiment, which resulted in higher final live weight (P < 0.05) in the phase when compared to the control treatment (24.34 kg and 21.55 kg, respectively). The animals that received probiotics showed an intermediate performance (23.66 kg final live weight) at the end of the 38 experimental days. Both additives were effective in increasing groups essential for intestinal health, such asRuminococcaceaeandLachnospiraceae. The functional oils were more effective in reducing pathogenic bacteria, such asCampylobacterandEscherichia coli. In conclusion, the use of functional oils optimized performance and effectively modulated the microbiota of newly weaned piglets.