bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suppression of 4.1R enhances the potency of NKG2D-CAR T cells against pancreatic carcinoma via activating ERK signaling pathway
Authors: Gao Yaoxin , Lin Haizhen , Guo Dandan , Cheng Sijia , Zhou Ying , Zhang Li , Yao Jie , Farooq Muhammad Asad , Ajmal Iqra , Duan Yixin , He Cong , Tao Lei , Wu Shijia , Liu Mingyao , Jiang Wenzheng 
Published: September 2021

AbstractPancreatic carcinoma (PC) is one of the most common malignancies. Chimeric antigen receptor (CAR)-modified T cells has achieved remarkable efficacy in the treatment of hematological malignancies. However, lack of tumor-specific targets and the existence of inhibitory factors limit the function of CAR T cells when treating solid tumors. 4.1R has been reported to suppress the anti-tumor activity of T cell responses. In this study, we investigated the anti-tumor activity of 4.1R deletion in natural killer group 2D (NKG2D)-CAR T cells against PC. The CAR T cells were obtained by transfecting T cells with lentiviral vector carrying NKG2D-CAR, NC-NKG2D-CAR, or KD2-NKG2D-CAR. In vitro, NKG2D-CAR T cells showed higher cytotoxicity than Mock T cells. However, compared to NKG2D-CAR T cells, furtherly higher cytotoxicity against PC cells in a dose-dependent manner was found in KD2-NKG2D-CAR T cells. In addition, the proliferation rate and cytotoxic activity of KD2-NKG2D-CAR T cells were significantly higher than those of NKG2D-CAR T cells. Besides, the inhibitory receptors PD-1 and TIM-3 were expressed in lower level on KD2-NKG2D-CAR T cells. In vivo, KD2-NKG2D-CAR T cells suppressed tumor growth more effectively in a xenograft model compared to NKG2D-CAR T cells. Mechanistically, 4.1R regulated CAR T cell function via activating ERK signaling pathway. Therefore, the study provides a new idea to enhance the anti-tumor efficiency of CAR T therapy.
Machine-learning-based diagnosis of drug-naive adult patients with attention-deficit hyperactivity disorder using mismatch negativity
Authors: Kim Sungkean , Baek Ji Hyun , Kwon Young Joon , Lee Hwa Young , Yoo Jae Hyun , Shim Se-hoon , Kim Ji Sun 
Published: September 2021

AbstractRelatively little is investigated regarding the neurophysiology of adult attention-deficit/hyperactivity disorder (ADHD). Mismatch negativity (MMN) is an event-related potential component representing pre-attentive auditory processing, which is closely associated with cognitive status. We investigated MMN features as biomarkers to classify drug-naive adult patients with ADHD and healthy controls (HCs). Sensor-level features (amplitude and latency) and source-level features (source activation) of MMN were investigated and compared between the electroencephalograms of 34 patients with ADHD and 45 HCs using a passive auditory oddball paradigm. Correlations between MMN features and ADHD symptoms were analyzed. Finally, we applied machine learning to differentiate the two groups using sensor- and source-level features of MMN. Adult patients with ADHD showed significantly lower MMN amplitudes at the frontocentral electrodes and reduced MMN source activation in the frontal, temporal, and limbic lobes, which were closely associated with MMN generators and ADHD pathophysiology. Source activities were significantly correlated with ADHD symptoms. The best classification performance for adult ADHD patients and HCs showed an 81.01% accuracy, 82.35% sensitivity, and 80.00% specificity based on MMN source activity features. Our results suggest that abnormal MMN reflects the adult ADHD patients’ pathophysiological characteristics and might serve clinically as a neuromarker of adult ADHD.
tRNA-derived small RNAs: novel regulators of cancer hallmarks and targets of clinical application
Authors: Li Xizhe , Liu Xianyu , Zhao Deze , Cui Weifang , Wu Yingfang , Zhang Chunfang , Duan Chaojun 
Published: September 2021

AbstracttRNAs are a group of conventional noncoding RNAs (ncRNAs) with critical roles in the biological synthesis of proteins. Recently, tRNA-derived small RNAs (tsRNAs) were found to have important biological functions in the development of human diseases including carcinomas, rather than just being considered pure degradation material. tsRNAs not only are abnormally expressed in the cancer tissues and serum of cancer patients, but also have been suggested to regulate various vital cancer hallmarks. On the other hand, the application of tsRNAs as biomarkers and therapeutic targets is promising. In this review, we focused on the basic characteristics of tsRNAs, and their biological functions known thus far, and explored the regulatory roles of tsRNAs in cancer hallmarks including proliferation, apoptosis, metastasis, tumor microenvironment, drug resistance, cancer stem cell phenotype, and cancer cell metabolism. In addition, we also discussed the research progress on the application of tsRNAs as tumor biomarkers and therapeutic targets.
Field-induced quantum spin disordered state in spin-1/2 honeycomb magnet Na2Co2TeO6
Authors: Lin Gaoting , Jeong Jaehong , Kim Chaebin , Wang Yao , Huang Qing , Masuda Takatsugu , Asai Shinichiro , Itoh Shinichi , Günther Gerrit , Russina Margarita , Lu Zhilun , Sheng Jieming , Wang Le , Wang Jiucai , Wang Guohua , Ren Qingyong , Xi Chuanying , Tong Wei , Ling Langsheng , Liu Zhengxin , Wu Liusuo , Mei Jiawei , Qu Zhe , Zhou Haidong , Wang Xiaoqun , Park Je-Geun , Wan Yuan , Ma Jie 
Published: September 2021

AbstractSpin-orbit coupled honeycomb magnets with the Kitaev interaction have received a lot of attention due to their potential of hosting exotic quantum states including quantum spin liquids. Thus far, the most studied Kitaev systems are 4d/5d-based honeycomb magnets. Recent theoretical studies predicted that 3d-based honeycomb magnets, including Na2Co2TeO6 (NCTO), could also be a potential Kitaev system. Here, we have used a combination of heat capacity, magnetization, electron spin resonance measurements alongside inelastic neutron scattering (INS) to study NCTO’s quantum magnetism, and we have found a field-induced spin disordered state in an applied magnetic field range of 7.5 T < B (⊥ b-axis) < 10.5 T. The INS spectra were also simulated to tentatively extract the exchange interactions. As a 3d-magnet with a field-induced disordered state on an effective spin-1/2 honeycomb lattice, NCTO expands the Kitaev model to 3d compounds, promoting further interests on the spin-orbital effect in quantum magnets.
Characterising proteolysis during SARS-CoV-2 infection identifies viral cleavage sites and cellular targets with therapeutic potential
Authors: Meyer Bjoern , Chiaravalli Jeanne , Gellenoncourt Stacy , Brownridge Philip , Bryne Dominic P. , Daly Leonard A. , Grauslys Arturas , Walter Marius , Agou Fabrice , Chakrabarti Lisa A. , Craik Charles S. , Eyers Claire E. , Eyers Patrick A. , Gambin Yann , Jones Andrew R. , Sierecki Emma , Verdin Eric , Vignuzzi Marco , Emmott Edward 
Published: September 2021

AbstractSARS-CoV-2 is the causative agent behind the COVID-19 pandemic, responsible for over 170 million infections, and over 3.7 million deaths worldwide. Efforts to test, treat and vaccinate against this pathogen all benefit from an improved understanding of the basic biology of SARS-CoV-2. Both viral and cellular proteases play a crucial role in SARS-CoV-2 replication. Here, we study proteolytic cleavage of viral and cellular proteins in two cell line models of SARS-CoV-2 replication using mass spectrometry to identify protein neo-N-termini generated through protease activity. We identify previously unknown cleavage sites in multiple viral proteins, including major antigens S and N: the main targets for vaccine and antibody testing efforts. We discover significant increases in cellular cleavage events consistent with cleavage by SARS-CoV-2 main protease, and identify 14 potential high-confidence substrates of the main and papain-like proteases. We show that siRNA depletion of these cellular proteins inhibits SARS-CoV-2 replication, and that drugs targeting two of these proteins: the tyrosine kinase SRC and Ser/Thr kinase MYLK, show a dose-dependent reduction in SARS-CoV-2 titres. Overall, our study provides a powerful resource to understand proteolysis in the context of viral infection, and to inform the development of targeted strategies to inhibit SARS-CoV-2 and treat COVID-19.
Next generation reservoir computing
Authors: Gauthier Daniel J. , Bollt Erik , Griffith Aaron , Barbosa Wendson A. S. 
Published: September 2021

AbstractReservoir computing is a best-in-class machine learning algorithm for processing information generated by dynamical systems using observed time-series data. Importantly, it requires very small training data sets, uses linear optimization, and thus requires minimal computing resources. However, the algorithm uses randomly sampled matrices to define the underlying recurrent neural network and has a multitude of metaparameters that must be optimized. Recent results demonstrate the equivalence of reservoir computing to nonlinear vector autoregression, which requires no random matrices, fewer metaparameters, and provides interpretable results. Here, we demonstrate that nonlinear vector autoregression excels at reservoir computing benchmark tasks and requires even shorter training data sets and training time, heralding the next generation of reservoir computing.
NAD+ augmentation with nicotinamide riboside improves lymphoid potential of Atm−/− and old mice HSCs
Authors: Zong Le , Tanaka-Yano Mayuri , Park Bongsoo , Yanai Hagai , Turhan Ferda T. , Croteau Deborah L. , Tian Jane , Fang Evandro F. , Bohr Vilhelm A. , Beerman Isabel 
Published: September 2021

AbstractNAD+ supplementation has significant benefits in compromised settings, acting largely through improved mitochondrial function and DNA repair. Elevating NAD+ to physiological levels has been shown to improve the function of some adult stem cells, with implications that these changes will lead to sustained improvement of the tissue or system. Here, we examined the effect of elevating NAD+ levels in models with reduced hematopoietic stem cell (HSC) potential, ATM-deficient and aged WT mice, and showed that supplementation of nicotinamide riboside (NR), a NAD+ precursor, improved lymphoid lineage potential during supplementation. In aged mice, this improved lymphoid potential was maintained in competitive transplants and was associated with transcriptional repression of myeloid gene signatures in stem and lineage-committed progenitor cells after NR treatment. However, the altered transcriptional priming of the stem cells toward lymphoid lineages was not sustained in the aged mice after NR removal. These data characterize significant alterations to the lineage potential of functionally compromised HSCs after short-term exposure to NR treatment.
Predicting cancer drug TARGETS - TreAtment Response Generalized Elastic-neT Signatures
Authors: Rydzewski Nicholas R. , Peterson Erik , Lang Joshua M. , Yu Menggang , Laura Chang S. , Sjöström Martin , Bakhtiar Hamza , Song Gefei , Helzer Kyle T. , Bootsma Matthew L. , Chen William S. , Shrestha Raunak M. , Zhang Meng , Quigley David A. , Aggarwal Rahul , Small Eric J. , Wahl Daniel R. , Feng Felix Y. , Zhao Shuang G. 
Published: September 2021

AbstractWe are now in an era of molecular medicine, where specific DNA alterations can be used to identify patients who will respond to specific drugs. However, there are only a handful of clinically used predictive biomarkers in oncology. Herein, we describe an approach utilizing in vitro DNA and RNA sequencing and drug response data to create TreAtment Response Generalized Elastic-neT Signatures (TARGETS). We trained TARGETS drug response models using Elastic-Net regression in the publicly available Genomics of Drug Sensitivity in Cancer (GDSC) database. Models were then validated on additional in-vitro data from the Cancer Cell Line Encyclopedia (CCLE), and on clinical samples from The Cancer Genome Atlas (TCGA) and Stand Up to Cancer/Prostate Cancer Foundation West Coast Prostate Cancer Dream Team (WCDT). First, we demonstrated that all TARGETS models successfully predicted treatment response in the separate in-vitro CCLE treatment response dataset. Next, we evaluated all FDA-approved biomarker-based cancer drug indications in TCGA and demonstrated that TARGETS predictions were concordant with established clinical indications. Finally, we performed independent clinical validation in the WCDT and found that the TARGETS AR signaling inhibitors (ARSI) signature successfully predicted clinical treatment response in metastatic castration-resistant prostate cancer with a statistically significant interaction between the TARGETS score and PSA response (p = 0.0252). TARGETS represents a pan-cancer, platform-independent approach to predict response to oncologic therapies and could be used as a tool to better select patients for existing therapies as well as identify new indications for testing in prospective clinical trials.
Pathways to Parkinson’s disease: a spotlight on 14-3-3 proteins
Authors: Giusto E. , Yacoubian T. A. , Greggio E. , Civiero L. 
Published: September 2021

Abstract14-3-3s represent a family of highly conserved 30 kDa acidic proteins. 14-3-3s recognize and bind specific phospho-sequences on client partners and operate as molecular hubs to regulate their activity, localization, folding, degradation, and protein–protein interactions. 14-3-3s are also associated with the pathogenesis of several diseases, among which Parkinson’s disease (PD). 14-3-3s are found within Lewy bodies (LBs) in PD patients, and their neuroprotective effects have been demonstrated in several animal models of PD. Notably, 14-3-3s interact with some of the major proteins known to be involved in the pathogenesis of PD. Here we first provide a detailed overview of the molecular composition and structural features of 14-3-3s, laying significant emphasis on their peculiar target-binding mechanisms. We then briefly describe the implication of 14-3-3s in the central nervous system and focus on their interaction with LRRK2, α-Synuclein, and Parkin, three of the major players in PD onset and progression. We finally discuss how different types of small molecules may interfere with 14-3-3s interactome, thus representing a valid strategy in the future of drug discovery.
Early EEG responses to pre-electoral survey items reflect political attitudes and predict voting behavior
Authors: Galli Giulia , Angelucci Davide , Bode Stefan , De Giorgi Chiara , De Sio Lorenzo , Paparo Aldo , Di Lorenzo Giorgio , Betti Viviana 
Published: September 2021

AbstractSelf-reports are conventionally used to measure political preferences, yet individuals may be unable or unwilling to report their political attitudes. Here, in 69 participants we compared implicit and explicit methods of political attitude assessment and focused our investigation on populist attitudes. Ahead of the 2019 European Parliament election, we recorded electroencephalography (EEG) from future voters while they completed a survey that measured levels of agreement on different political issues. An Implicit Association Test (IAT) was administered at the end of the recording session. Neural signals differed as a function of future vote for a populist or mainstream party and of whether survey items expressed populist or non-populist views. The combination of EEG responses and self-reported preferences predicted electoral choice better than traditional socio-demographic and ideological variables, while IAT scores were not a significant predictor. These findings suggest that measurements of brain activity can refine the assessment of socio-political attitudes, even when those attitudes are not based on traditional ideological divides.
Real-time observation of nucleation and growth of Au on CdSe quantum dot templates
Authors: Paul Neelima , Huang Junyu , Liu Chang , Lin Taidong , Ouyang Chenghao , Liu Zhaoyu , Chen Chunfeng , Chen Zhongyi , Weng Zhiyin , Schwartzkopf Matthias , Roth Stephan V. , Müller-Buschbaum Peter , Paul Amitesh 
Published: September 2021

AbstractSemiconductor quantum dot (QD) arrays can be useful for optical devices such as lasers, solar cells and light-emitting diodes. As the size distribution influences the band-gap, it is worthwhile to investigate QDs prepared using different solvents because each of them could influence the overall morphology differently, depending on the ligand network around individual QDs. Here, we follow the nucleation and growth of gold (Au) on CdSe QD arrays to investigate the influence of surface ligands and thereby realized interparticle distance between QDs on Au growth behaviour. We particularly emphasize on the monolayer stage as the Au decoration on individual QDs is expected at this stage. Therefore, we sputter-deposit Au on each QD array to investigate the morphological evolution in real-time using time-resolved grazing-incidence small-angle X-ray scattering (GISAXS). The growth kinetics - independent of the template - signifies that the observed template-mediated nucleation is limited only to the very first few monolayers. Delicate changes in the Au growth morphology are seen in the immediate steps following the initial replicated decoration of the QD arrays. This is followed by a subsequent clustering and finally a complete Au coverage of the QD arrays.
Decomposition of peatland DOC affected by root exudates is driven by specific r and K strategic bacterial taxa
Authors: Mastný Jiří , Bárta Jiří , Kaštovská Eva , Picek Tomáš 
Published: September 2021

AbstractIn peatlands, decomposition of organic matter is limited by harsh environmental conditions and low decomposability of the plant material. Shifting vegetation composition fromSphagnumtowards vascular plants is expected in response to climate change, which will lead to increased root exudate flux to the soil and stimulation of microbial growth and activity. We aimed to evaluate the effect of root exudates on the decomposition of recalcitrant dissolved organic carbon (DOC) and to identify microorganisms involved in this process. The exudation was mimicked by an addition of a mixture of13C labelled compounds into the recalcitrant DOC in two realistic levels; 2% and 5% of total DOC and peatland porewater with added root exudates was incubated under controlled conditions in the lab. The early stage of incubation was characterized by a relative increase of r-strategic bacteria mainly fromGammaproteobacteriaandBacteriodetes phyla within the microbial community and their preferential use of the added compounds. At the later stage,AlphaproteobacteriaandAcidobacteriamembers were the dominating phyla, which metabolized both the transformed13C compounds and the recalcitrant DOC. Only higher exudate input (5% of total DOC) stimulated decomposition of recalcitrant DOC compared to non-amended control. The most important taxa with a potential to decompose complex DOC compounds were identified as:Mucilaginibacter(Bacteriodetes),BurkholderiaandPseudomonas(Gammaproteobacteria) among r-strategists andBryocellaandCandidatus Solibacter(Acidobacteria) among K-strategists. We conclude that increased root exudate inputs and their increasing C/N ratio stimulate growth and degradation potential of both r-strategic and K-strategic bacteria, which make the system more dynamic and may accelerate decomposition of peatland recalcitrant DOC.
Tetraploids expanded beyond the mountain niche of their diploid ancestors in the mixed-ploidy grass Festuca amethystina L.
Authors: Kiedrzyński Marcin , Zielińska Katarzyna M. , Jedrzejczyk Iwona , Kiedrzyńska Edyta , Tomczyk Przemysław P. , Rewicz Agnieszka , Rewers Monika , Indreica Adrian , Bednarska Iryna , Stupar Vladimir , Roleček Jan , Šmarda Petr 
Published: September 2021

AbstractOne promising area in understanding the responses of plants to ongoing global climate change is the adaptative effect of polyploidy. This work examines whether there is a coupling between the distribution of cytotypes and their biogeographical niche, and how different niches will affect their potential range. The study uses a range of techniques including flow cytometry, gradient and niche analysis, as well as distribution modelling. In addition, climatic, edaphic and habitat data was used to analyse environmental patterns and potential ranges of cytotypes in the first wide-range study ofFestuca amethystina—a mixed-ploidy mountain grass. The populations were found to be ploidy homogeneous and demonstrate a parapatric pattern of cytotype distribution. Potential contact zones have been identified. The tetraploids have a geographically broader distribution than diploids; they also tend to occur at lower altitudes and grow in more diverse climates, geological units and habitats. Moreover, tetraploids have a more extensive potential range, being six-fold larger than diploids. Montane pine forests were found to be a focal environment suitable for both cytotypes, which has a central place in the environmental space of the whole species. Our findings present polyploidy as a visible driver of geographical, ecological and adaptive variation within the species.
Quantitative assessment of the vertebral pneumaticity in an anhanguerid pterosaur using micro-CT ﻿scanning
Authors: Buchmann Richard , Holgado Borja , Sobral Gabriela , dos Santos Avilla Leonardo , Rodrigues Taissa 
Published: September 2021

AbstractResearch on the postcranial skeletal pneumaticity in pterosaurs is common in the literature, but most studies present only qualitative assessments. When quantitative, they are done on isolated bones. Here, we estimate the Air Space Proportion (ASP) obtained from micro-CT scans of the sequence from the sixth cervical to the fourth dorsal vertebra of an anhanguerine pterosaur to understand how pneumaticity is distributed in these bones. Pneumatisation of the vertebrae varied between 68 and 72% of their total volume. The neural arch showed higher ASP in all vertebrae. Anhanguerine vertebral ASP was generally higher than in sauropod vertebrae but lower than in most extant birds. The ASP observed here is lower than that calculated for the appendicular skeleton of other anhanguerian pterosaurs, indicating the potential existence of variation between axial and appendicular pneumatisation. The results point to a pattern in the distribution of the air space, which shows an increase in the area occupied by the trabecular bone in the craniocaudal direction of the vertebral series and, in each vertebra, an increase of the thickness of the trabeculae in the zygapophyses. This indicates that the distribution of pneumatic diverticula in anhanguerine vertebrae may not be associated with stochastic patterns.
Biomarkers of cellular aging during a controlled human malaria infection
Authors: Miglar Aurelie , Reuling Isaie J. , Yap Xi Zen , Färnert Anna , Sauerwein Robert W. , Asghar Muhammad 
Published: September 2021

AbstractCellular aging is difficult to study in individuals with natural infection, given the diversity of symptom duration and clinical presentation, and the high interference of aging-related processes with host and environmental factors. To address this challenge, we took advantage of the controlled human malaria infection (CHMI) model. This approach allowed us to characterize the relationship among cellular aging markers prior, during and post malaria pathophysiology in humans, controlling for infection dose, individual heterogeneity, previous exposure and co-infections. We demonstrate that already low levels ofPlasmodium falciparumimpact cellular aging by inducing high levels of inflammation and redox-imbalance; and that cellular senescence reversed after treatment and parasite clearance. This study provides insights into the complex relationship of telomere length, cellular senescence, telomerase expression and aging-related processes during a single malaria infection.