bluuebunny/crossref_metadata_2025_split huggingface dataset:
Place fields of single spikes in hippocampus involve Kcnq3 channel-dependent entrainment of complex spike bursts
Authors: Gao Xiaojie , Bender Franziska , Soh Heun , Chen Changwan , Altafi Mahsa , Schütze Sebastian , Heidenreich Matthias , Gorbati Maria , Corbu Mihaela-Anca , Carus-Cadavieco Marta , Korotkova Tatiana , Tzingounis Anastasios V. , Jentsch Thomas J. , Ponomarenko Alexey 
Published: August 2021

AbstractHippocampal pyramidal cells encode an animal’s location by single action potentials and complex spike bursts. These elementary signals are believed to play distinct roles in memory consolidation. The timing of single spikes and bursts is determined by intrinsic excitability and theta oscillations (5–10 Hz). Yet contributions of these dynamics to place fields remain elusive due to the lack of methods for specific modification of burst discharge. In mice lacking Kcnq3-containing M-type K+ channels, we find that pyramidal cell bursts are less coordinated by the theta rhythm than in controls during spatial navigation, but not alert immobility. Less modulated bursts are followed by an intact post-burst pause of single spike firing, resulting in a temporal discoordination of network oscillatory and intrinsic excitability. Place fields of single spikes in one- and two-dimensional environments are smaller in the mutant. Optogenetic manipulations of upstream signals reveal that neither medial septal GABA-ergic nor cholinergic inputs alone, but rather their joint activity, is required for entrainment of bursts. Our results suggest that altered representations by bursts and single spikes may contribute to deficits underlying cognitive disabilities associated with KCNQ3-mutations in humans.
Two parallel pathways connect glutamine metabolism and mTORC1 activity to regulate glutamoptosis
Authors: Bodineau Clément , Tomé Mercedes , Courtois Sarah , Costa Ana S. H. , Sciacovelli Marco , Rousseau Benoit , Richard Elodie , Vacher Pierre , Parejo-Pérez Carlos , Bessede Emilie , Varon Christine , Soubeyran Pierre , Frezza Christian , Murdoch Piedad del Socorro , Villar Victor H. , Durán Raúl V. 
Published: August 2021

AbstractGlutamoptosis is the induction of apoptotic cell death as a consequence of the aberrant activation of glutaminolysis and mTORC1 signaling during nutritional imbalance in proliferating cells. The role of the bioenergetic sensor AMPK during glutamoptosis is not defined yet. Here, we show that AMPK reactivation blocks both the glutamine-dependent activation of mTORC1 and glutamoptosis in vitro and in vivo. We also show that glutamine is used for asparagine synthesis and the GABA shunt to produce ATP and to inhibit AMPK, independently of glutaminolysis. Overall, our results indicate that glutamine metabolism is connected with mTORC1 activation through two parallel pathways: an acute alpha-ketoglutarate-dependent pathway; and a secondary ATP/AMPK-dependent pathway. This dual metabolic connection between glutamine and mTORC1 must be considered for the future design of therapeutic strategies to prevent cell growth in diseases such as cancer.
Manipulating crystallization dynamics through chelating molecules for bright perovskite emitters
Authors: Zou Yatao , Teng Pengpeng , Xu Weidong , Zheng Guanhaojie , Lin Weihua , Yin Jun , Kobera Libor , Abbrent Sabina , Li Xiangchun , Steele Julian A. , Solano Eduardo , Roeffaers Maarten B. J. , Li Jun , Cai Lei , Kuang Chaoyang , Scheblykin Ivan G. , Brus Jiri , Zheng Kaibo , Yang Ying , Mohammed Omar F. , Bakr Osman M. , Pullerits Tönu , Bai Sai , Sun Baoquan , Gao Feng 
Published: August 2021

AbstractMolecular additives are widely utilized to minimize non-radiative recombination in metal halide perovskite emitters due to their passivation effects from chemical bonds with ionic defects. However, a general and puzzling observation that can hardly be rationalized by passivation alone is that most of the molecular additives enabling high-efficiency perovskite light-emitting diodes (PeLEDs) are chelating (multidentate) molecules, while their respective monodentate counterparts receive limited attention. Here, we reveal the largely ignored yet critical role of the chelate effect on governing crystallization dynamics of perovskite emitters and mitigating trap-mediated non-radiative losses. Specifically, we discover that the chelate effect enhances lead-additive coordination affinity, enabling the formation of thermodynamically stable intermediate phases and inhibiting halide coordination-driven perovskite nucleation. The retarded perovskite nucleation and crystal growth are key to high crystal quality and thus efficient electroluminescence. Our work elucidates the full effects of molecular additives on PeLEDs by uncovering the chelate effect as an important feature within perovskite crystallization. As such, we open new prospects for the rationalized screening of highly effective molecular additives.
Chronological genome and single-cell transcriptome integration characterizes the evolutionary process of adult T cell leukemia-lymphoma
Authors: Yamagishi Makoto , Kubokawa Miyuki , Kuze Yuta , Suzuki Ayako , Yokomizo Akari , Kobayashi Seiichiro , Nakashima Makoto , Makiyama Junya , Iwanaga Masako , Fukuda Takahiro , Watanabe Toshiki , Suzuki Yutaka , Uchimaru Kaoru 
Published: August 2021

AbstractSubclonal genetic heterogeneity and their diverse gene expression impose serious problems in understanding the behavior of cancers and contemplating therapeutic strategies. Here we develop and utilize a capture-based sequencing panel, which covers host hotspot genes and the full-length genome of human T-cell leukemia virus type-1 (HTLV-1), to investigate the clonal architecture of adult T-cell leukemia-lymphoma (ATL). For chronologically collected specimens from patients with ATL or pre-onset individuals, we integrate deep DNA sequencing and single-cell RNA sequencing to detect the somatic mutations and virus directly and characterize the transcriptional readouts in respective subclones. Characteristic genomic and transcriptomic patterns are associated with subclonal expansion and switches during the clinical timeline. Multistep mutations in the T-cell receptor (TCR), STAT3, and NOTCH pathways establish clone-specific transcriptomic abnormalities and further accelerate their proliferative potential to develop highly malignant clones, leading to disease onset and progression. Early detection and characterization of newly expanded subclones through the integrative analytical platform will be valuable for the development of an in-depth understanding of this disease.
Altered function and differentiation of age-associated B cells contribute to the female bias in lupus mice
Authors: Ricker Edd , Manni Michela , Flores-Castro Danny , Jenkins Daniel , Gupta Sanjay , Rivera-Correa Juan , Meng Wenzhao , Rosenfeld Aaron M. , Pannellini Tania , Bachu Mahesh , Chinenov Yurii , Sculco Peter K. , Jessberger Rolf , Prak Eline T. Luning , Pernis Alessandra B. 
Published: August 2021

AbstractDifferences in immune responses to viruses and autoimmune diseases such as systemic lupus erythematosus (SLE) can show sexual dimorphism. Age-associated B cells (ABC) are a population of CD11c+T-bet+ B cells critical for antiviral responses and autoimmune disorders. Absence of DEF6 and SWAP-70, two homologous guanine exchange factors, in double-knock-out (DKO) mice leads to a lupus-like syndrome in females marked by accumulation of ABCs. Here we demonstrate that DKO ABCs show sex-specific differences in cell number, upregulation of an ISG signature, and further differentiation. DKO ABCs undergo oligoclonal expansion and differentiate into both CD11c+ and CD11c− effector B cell populations with pathogenic and pro-inflammatory function as demonstrated by BCR sequencing and fate-mapping experiments. Tlr7 duplication in DKO males overrides the sex-bias and further augments the dissemination and pathogenicity of ABCs, resulting in severe pulmonary inflammation and early mortality. Thus, sexual dimorphism shapes the expansion, function and differentiation of ABCs that accompanies TLR7-driven immunopathogenesis.
Emerging symmetric strain response and weakening nematic fluctuations in strongly hole-doped iron-based superconductors
Authors: Wiecki P. , Frachet M. , Haghighirad A.-A. , Wolf T. , Meingast C. , Heid R. , Böhmer A. E. 
Published: August 2021

AbstractElectronic nematicity is often found in unconventional superconductors, suggesting its relevance for electronic pairing. In the strongly hole-doped iron-based superconductors, the symmetry channel and strength of the nematic fluctuations, as well as the possible presence of long-range nematic order, remain controversial. Here, we address these questions using transport measurements under elastic strain. By decomposing the strain response into the appropriate symmetry channels, we demonstrate the emergence of a giant in-plane symmetric contribution, associated with the growth of both strong electronic correlations and the sensitivity of these correlations to strain. We find weakened remnants of the nematic fluctuations that are present at optimal doping, but no change in the symmetry channel of nematic fluctuations with hole doping. Furthermore, we find no indication of a nematic-ordered state in the AFe2As2 (A = K, Rb, Cs) superconductors. These results revise the current understanding of nematicity in hole-doped iron-based superconductors.
Predictive biomarkers for 5-fluorouracil and oxaliplatin-based chemotherapy in gastric cancers via profiling of patient-derived xenografts
Authors: Na Deukchae , Chae Jeesoo , Cho Sung-Yup , Kang Wonyoung , Lee Ahra , Min Seoyeon , Kang Jinjoo , Kim Min Jung , Choi Jaeyong , Lee Woochan , Shin Dongjin , Min Ahrum , Kim Yu-Jin , Lee Kyung-Hun , Kim Tae-Yong , Suh Yun-Suhk , Kong Seong-Ho , Lee Hyuk-Joon , Kim Woo-Ho , Park Hansoo , Im Seock-Ah , Yang Han-Kwang , Lee Charles , Kim Jong-Il 
Published: August 2021

AbstractGastric cancer (GC) is commonly treated by chemotherapy using 5-fluorouracil (5-FU) derivatives and platinum combination, but predictive biomarker remains lacking. We develop patient-derived xenografts (PDXs) from 31 GC patients and treat with a combination of 5-FU and oxaliplatin, to determine biomarkers associated with responsiveness. When the PDXs are defined as either responders or non-responders according to tumor volume change after treatment, the responsiveness of PDXs is significantly consistent with the respective clinical outcomes of the patients. An integrative genomic and transcriptomic analysis of PDXs reveals that pathways associated with cell-to-cell and cell-to-extracellular matrix interactions enriched among the non-responders in both cancer cells and the tumor microenvironment (TME). We develop a 30-gene prediction model to determine the responsiveness to 5-FU and oxaliplatin-based chemotherapy and confirm the significant poor survival outcomes among cases classified as non-responder-like in three independent GC cohorts. Our study may inform clinical decision-making when designing treatment strategies.
The molecular basis, genetic control and pleiotropic effects of local gene co-expression
Authors: Ribeiro Diogo M. , Rubinacci Simone , Ramisch Anna , Hofmeister Robin J. , Dermitzakis Emmanouil T. , Delaneau Olivier 
Published: August 2021

AbstractNearby genes are often expressed as a group. Yet, the prevalence, molecular mechanisms and genetic control of local gene co-expression are far from being understood. Here, by leveraging gene expression measurements across 49 human tissues and hundreds of individuals, we find that local gene co-expression occurs in 13% to 53% of genes per tissue. By integrating various molecular assays (e.g. ChIP-seq and Hi-C), we estimate the ability of several mechanisms, such as enhancer-gene interactions, in distinguishing gene pairs that are co-expressed from those that are not. Notably, we identify 32,636 expression quantitative trait loci (eQTLs) which associate with co-expressed gene pairs and often overlap enhancer regions. Due to affecting several genes, these eQTLs are more often associated with multiple human traits than other eQTLs. Our study paves the way to comprehend trait pleiotropy and functional interpretation of QTL and GWAS findings. All local gene co-expression identified here is available through a public database (https://glcoex.unil.ch/).
Sound trapping in an open resonator
Authors: Huang Lujun , Chiang Yan Kei , Huang Sibo , Shen Chen , Deng Fu , Cheng Yi , Jia Bin , Li Yong , Powell David A. , Miroshnichenko Andrey E. 
Published: August 2021

AbstractThe ability of sound energy confinement with high-quality factor resonance is of vital importance for acoustic devices requiring high intensity and hypersensitivity in biological ultrasonics, enhanced collimated sound emission (i.e. sound laser) and high-resolution sensing. However, structures reported so far have been experimentally demonstrated with a limited quality factor of acoustic resonances, up to several tens in an open resonator. The emergence of bound states in the continuum makes it possible to realize high quality factor acoustic modes. Here, we report the theoretical design and experimental demonstration of acoustic bound states in the continuum supported by a single open resonator. We predicted that such an open acoustic resonator could simultaneously support three types of bound states in the continuum, including symmetry protected bound states in the continuum, Friedrich-Wintgen bound states in the continuum induced by mode interference, as well as a new type-mirror symmetry induced bound states in the continuum. We also experimentally demonstrated their existence with quality factor up to one order of magnitude greater than the highest quality factor reported in an open resonator.
Tracking the introduction and spread of SARS-CoV-2 in coastal Kenya
Authors: Githinji George , de Laurent Zaydah R. , Mohammed Khadija Said , Omuoyo Donwilliams O. , Macharia Peter M. , Morobe John M. , Otieno Edward , Kinyanjui Samson M. , Agweyu Ambrose , Maitha Eric , Kitole Ben , Suleiman Thani , Mwakinangu Mohamed , Nyambu John , Otieno John , Salim Barke , Kasera Kadondi , Kiiru John , Aman Rashid , Barasa Edwine , Warimwe George , Bejon Philip , Tsofa Benjamin , Ochola-Oyier Lynette Isabella , Nokes D. James , Agoti Charles N. 
Published: August 2021

AbstractGenomic surveillance of SARS-CoV-2 is important for understanding both the evolution and the patterns of local and global transmission. Here, we generated 311 SARS-CoV-2 genomes from samples collected in coastal Kenya between 17th March and 31st July 2020. We estimated multiple independent SARS-CoV-2 introductions into the region were primarily of European origin, although introductions could have come through neighbouring countries. Lineage B.1 accounted for 74% of sequenced cases. Lineages A, B and B.4 were detected in screened individuals at the Kenya-Tanzania border or returning travellers. Though multiple lineages were introduced into coastal Kenya following the initial confirmed case, none showed extensive local expansion other than lineage B.1. International points of entry were important conduits of SARS-CoV-2 importations into coastal Kenya and early public health responses prevented established transmission of some lineages. Undetected introductions through points of entry including imports from elsewhere in the country gave rise to the local epidemic at the Kenyan coast.
Theta-phase dependent neuronal coding during sequence learning in human single neurons
Authors: Reddy Leila , Self Matthew W. , Zoefel Benedikt , Poncet Marlène , Possel Jessy K. , Peters Judith C. , Baayen Johannes C. , Idema Sander , VanRullen Rufin , Roelfsema Pieter R. 
Published: August 2021

AbstractThe ability to maintain a sequence of items in memory is a fundamental cognitive function. In the rodent hippocampus, the representation of sequentially organized spatial locations is reflected by the phase of action potentials relative to the theta oscillation (phase precession). We investigated whether the timing of neuronal activity relative to the theta brain oscillation also reflects sequence order in the medial temporal lobe of humans. We used a task in which human participants learned a fixed sequence of pictures and recorded single neuron and local field potential activity with implanted electrodes. We report that spikes for three consecutive items in the sequence (the preferred stimulus for each cell, as well as the stimuli immediately preceding and following it) were phase-locked at distinct phases of the theta oscillation. Consistent with phase precession, spikes were fired at progressively earlier phases as the sequence advanced. These findings generalize previous findings in the rodent hippocampus to the human temporal lobe and suggest that encoding stimulus information at distinct oscillatory phases may play a role in maintaining sequential order in memory.
Small tandem DNA duplications result from CST-guided Pol α-primase action at DNA break termini
Authors: Schimmel Joost , Muñoz-Subirana Núria , Kool Hanneke , van Schendel Robin , Tijsterman Marcel 
Published: August 2021

AbstractSmall tandem duplications of DNA occur frequently in the human genome and are implicated in the aetiology of certain human cancers. Recent studies have suggested that DNA double-strand breaks are causal to this mutational class, but the underlying mechanism remains elusive. Here, we identify a crucial role for DNA polymerase α (Pol α)-primase in tandem duplication formation at breaks having complementary 3′ ssDNA protrusions. By including so-called primase deserts in CRISPR/Cas9-induced DNA break configurations, we reveal that fill-in synthesis preferentially starts at the 3′ tip, and find this activity to be dependent on 53BP1, and the CTC1-STN1-TEN1 (CST) and Shieldin complexes. This axis generates near-blunt ends specifically at DNA breaks with 3′ overhangs, which are subsequently repaired by non-homologous end-joining. Our study provides a mechanistic explanation for a mutational signature abundantly observed in the genomes of species and cancer cells.
Exciton-driven antiferromagnetic metal in a correlated van der Waals insulator
Authors: Belvin Carina A. , Baldini Edoardo , Ozel Ilkem Ozge , Mao Dan , Po Hoi Chun , Allington Clifford J. , Son Suhan , Kim Beom Hyun , Kim Jonghyeon , Hwang Inho , Kim Jae Hoon , Park Je-Geun , Senthil T. , Gedik Nuh 
Published: August 2021

AbstractCollective excitations of bound electron-hole pairs—known as excitons—are ubiquitous in condensed matter, emerging in systems as diverse as band semiconductors, molecular crystals, and proteins. Recently, their existence in strongly correlated electron materials has attracted increasing interest due to the excitons’ unique coupling to spin and orbital degrees of freedom. The non-equilibrium driving of such dressed quasiparticles offers a promising platform for realizing unconventional many-body phenomena and phases beyond thermodynamic equilibrium. Here, we achieve this in the van der Waals correlated insulator NiPS3 by photoexciting its newly discovered spin–orbit-entangled excitons that arise from Zhang-Rice states. By monitoring the time evolution of the terahertz conductivity, we observe the coexistence of itinerant carriers produced by exciton dissociation and a long-wavelength antiferromagnetic magnon that coherently precesses in time. These results demonstrate the emergence of a transient metallic state that preserves long-range antiferromagnetism, a phase that cannot be reached by simply tuning the temperature. More broadly, our findings open an avenue toward the exciton-mediated optical manipulation of magnetism.
Myocardial fibrosis reversion via rhACE2-electrospun fibrous patch for ventricular remodeling prevention
Authors: Qiu Zeping , Zhao Jingwen , Huang Fanyi , Bao Luhan , Chen Yanjia , Yang Ke , Cui Wenguo , Jin Wei 
Published: August 2021

AbstractMyocardial fibrosis and ventricular remodeling were the key pathology factors causing undesirable consequence after myocardial infarction. However, an efficient therapeutic method remains unclear, partly due to difficulty in continuously preventing neurohormonal overactivation and potential disadvantages of cell therapy for clinical practice. In this study, a rhACE2-electrospun fibrous patch with sustained releasing of rhACE2 to shape an induction transformation niche in situ was introduced, through micro-sol electrospinning technologies. A durable releasing pattern of rhACE2 encapsulated in hyaluronic acid (HA)—poly(L-lactic acid) (PLLA) core-shell structure was observed. By multiple in vitro studies, the rhACE2 patch demonstrated effectiveness in reducing cardiomyocytes apoptosis under hypoxia stress and inhibiting cardiac fibroblasts proliferation, which gave evidence for its in vivo efficacy. For striking mice myocardial infarction experiments, a successful prevention of adverse ventricular remodeling has been demonstrated, reflecting by improved ejection fraction, normal ventricle structure and less fibrosis. The rhACE2 patch niche showed clear superiority in long term function and structure preservation after ischemia compared with intramyocardial injection. Thus, the micro-sol electrospun rhACE2 fibrous patch niche was proved to be efficient, cost-effective and easy-to-use in preventing ventricular adverse remodeling.
Identification of prognostic biomarkers related to the tumor microenvironment in thyroid carcinoma
Authors: Du Jun-wei , Li Guo-quan , Li Yang-sen , Qiu Xin-guang 
Published: August 2021

AbstractThyroid Carcinoma (THCA) is the most common endocrine tumor that is mainly treated using surgery and radiotherapy. In addition, immunotherapy is a recently developed treatment option that has played an essential role in the management of several types of tumors. However, few reports exist on the use of immunotherapy to treat THCA. The study downloaded the miRNA, mRNA and lncRNA data for THCA patients from the TCGA database (https://portal.gdc.cancer.gov/). Thereafter, the tumor samples were divided into cold and hot tumors, based on the immune score of the tumor microenvironment. Moreover, the differentially expressed lncRNAs and miRNAs were obtained. Finally, the study jointly constructed a ceRNA network through differential analysis of the mRNA data for cold and hot tumors. The study first assessed the level of immune infiltration in the THCA tumor microenvironment then divided the samples into cold and hot tumors, based on the immune score. Additionally, a total of 568 up-regulated and 412 down-regulated DEGs were screened by analyzing the differences between hot and cold tumors. Thereafter, the study examined the differentially expressed genes for lncRNA and miRNA. The results revealed 629 differentially expressed genes related to lncRNA and 114 associated with miRNA. Finally, a ceRNA network of the differentially expressed genes was constructed. The results showed a five-miRNA hubnet, i.e., hsa-mir-204, hsa-mir-128, hsa-mir-214, hsa-mir-150 and hsa-mir-338. The present study identified the immune-related mRNA, lncRNA and miRNA in THCA then constructed a ceRNA network. These results are therefore important as they provide more insights on the immune mechanisms in THCA. The findings also provides additional information for possible THCA immunotherapy.