bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-modal molecular programs regulate melanoma cell state
Authors: Andrews Miles C. , Oba Junna , Wu Chang-Jiun , Zhu Haifeng , Karpinets Tatiana , Creasy Caitlin A. , Forget Marie-Andrée , Yu Xiaoxing , Song Xingzhi , Mao Xizeng , Robertson A. Gordon , Romano Gabriele , Li Peng , Burton Elizabeth M. , Lu Yiling , Sloane Robert Szczepaniak , Wani Khalida M. , Rai Kunal , Lazar Alexander J. , Haydu Lauren E. , Bustos Matias A. , Shen Jianjun , Chen Yueping , Morgan Margaret B. , Wargo Jennifer A. , Kwong Lawrence N. , Haymaker Cara L. , Grimm Elizabeth A. , Hwu Patrick , Hoon Dave S. B. , Zhang Jianhua , Gershenwald Jeffrey E. , Davies Michael A. , Futreal P. Andrew , Bernatchez Chantale , Woodman Scott E. 
Published: July 2022

AbstractMelanoma cells display distinct intrinsic phenotypic states. Here, we seek to characterize the molecular regulation of these states using multi-omic analyses of whole exome, transcriptome, microRNA, long non-coding RNA and DNA methylation data together with reverse-phase protein array data on a panel of 68 highly annotated early passage melanoma cell lines. We demonstrate that clearly defined cancer cell intrinsic transcriptomic programs are maintained in melanoma cells ex vivo and remain highly conserved within melanoma tumors, are associated with distinct immune features within tumors, and differentially correlate with checkpoint inhibitor and adoptive T cell therapy efficacy. Through integrative analyses we demonstrate highly complex multi-omic regulation of melanoma cell intrinsic programs that provide key insights into the molecular maintenance of phenotypic states. These findings have implications for cancer biology and the identification of new therapeutic strategies. Further, these deeply characterized cell lines will serve as an invaluable resource for future research in the field.
ADAMTS18+ villus tip telocytes maintain a polarized VEGFA signaling domain and fenestrations in nutrient-absorbing intestinal blood vessels
Authors: Bernier-Latmani Jeremiah , Mauri Cristina , Marcone Rachel , Renevey François , Durot Stephan , He Liqun , Vanlandewijck Michael , Maclachlan Catherine , Davanture Suzel , Zamboni Nicola , Knott Graham W. , Luther Sanjiv A. , Betsholtz Christer , Delorenzi Mauro , Brisken Cathrin , Petrova Tatiana V. 
Published: July 2022

AbstractThe small intestinal villus tip is the first point of contact for lumen-derived substances including nutrients and microbial products. Electron microscopy studies from the early 1970s uncovered unusual spatial organization of small intestinal villus tip blood vessels: their exterior, epithelial-facing side is fenestrated, while the side facing the villus stroma is non-fenestrated, covered by pericytes and harbors endothelial nuclei. Such organization optimizes the absorption process, however the molecular mechanisms maintaining this highly specialized structure remain unclear. Here we report that perivascular LGR5+ villus tip telocytes (VTTs) are necessary for maintenance of villus tip endothelial cell polarization and fenestration by sequestering VEGFA signaling. Mechanistically, unique VTT expression of the protease ADAMTS18 is necessary for VEGFA signaling sequestration through limiting fibronectin accumulation. Therefore, we propose a model in which LGR5+ ADAMTS18+telocytes are necessary to maintain a “just-right” level and location of VEGFA signaling in intestinal villus blood vasculature to ensure on one hand the presence of sufficient endothelial fenestrae, while avoiding excessive leakiness of the vessels and destabilization of villus tip epithelial structures.
Photonic-circuited resonance fluorescence of single molecules with an ultrastable lifetime-limited transition
Authors: Ren Penglong , Wei Shangming , Liu Weixi , Lin Shupei , Tian Zhaohua , Huang Tailin , Tang Jianwei , Shi Yaocheng , Chen Xue-Wen 
Published: July 2022

AbstractResonance fluorescence as the emission of a resonantly-excited two-level quantum system promises indistinguishable single photons and coherent high-fidelity quantum-state manipulation of the matter qubit, which underpin many quantum information processing protocols. Real applications of the protocols demand high degrees of scalability and stability of the experimental platform, and thus favor quantum systems integrated on one chip. However, the on-chip solution confronts several formidable challenges compromising the scalability prospect, such as the randomness, spectral wandering and scattering background of the integrated quantum systems near heterogeneous and nanofabricated material interfaces. Here we report an organic-inorganic hybrid integrated quantum photonic platform that circuits background-free resonance fluorescence of single molecules with an ultrastable lifetime-limited transition. Our platform allows a collective alignment of the dipole orientations of many isolated molecules with the photonic waveguide. We demonstrate on-chip generation, beam splitting and routing of resonance-fluorescence single photons with a signal-to-background ratio over 3000 in the waveguide at the weak excitation limit. Crucially, we show the photonic-circuited single molecules possess a lifetime-limited-linewidth transition and exhibit inhomogeneous spectral broadenings of only about 5% over hours’ measurements. These findings and the versatility of our platform pave the way for scalable quantum photonic networks.
Variance-quantitative trait loci enable systematic discovery of gene-environment interactions for cardiometabolic serum biomarkers
Authors: Westerman Kenneth E. , Majarian Timothy D. , Giulianini Franco , Jang Dong-Keun , Miao Jenkai , Florez Jose C. , Chen Han , Chasman Daniel I. , Udler Miriam S. , Manning Alisa K. , Cole Joanne B. 
Published: July 2022

AbstractGene-environment interactions represent the modification of genetic effects by environmental exposures and are critical for understanding disease and informing personalized medicine. These often induce differential phenotypic variance across genotypes; these variance-quantitative trait loci can be prioritized in a two-stage interaction detection strategy to greatly reduce the computational and statistical burden and enable testing of a broader range of exposures. We perform genome-wide variance-quantitative trait locus analysis for 20 serum cardiometabolic biomarkers by multi-ancestry meta-analysis of 350,016 unrelated participants in the UK Biobank, identifying 182 independent locus-biomarker pairs (p < 4.5×10−9). Most are concentrated in a small subset (4%) of loci with genome-wide significant main effects, and 44% replicate (p < 0.05) in the Women’s Genome Health Study (N = 23,294). Next, we test each locus-biomarker pair for interaction across 2380 exposures, identifying 847 significant interactions (p < 2.4×10−7), of which 132 are independent (p < 0.05) after accounting for correlation between exposures. Specific examples demonstrate interaction of triglyceride-associated variants with distinct body mass- versus body fat-related exposures as well as genotype-specific associations between alcohol consumption and liver stress at the ADH1B gene. Our catalog of variance-quantitative trait loci and gene-environment interactions is publicly available in an online portal.
All-fibre heterogeneously-integrated frequency comb generation using silicon core fibre
Authors: Sohanpal Ronit , Ren Haonan , Shen Li , Deakin Callum , Heidt Alexander M. , Hawkins Thomas W. , Ballato John , Gibson Ursula J. , Peacock Anna C. , Liu Zhixin 
Published: July 2022

AbstractOriginally developed for metrology, optical frequency combs are becoming increasingly pervasive in a wider range of research topics including optical communications, spectroscopy, and radio or microwave signal processing. However, application demands in these fields can be more challenging as they require compact sources with a high tolerance to temperature variations that are capable of delivering flat comb spectra, high power per tone, narrow linewidth and high optical signal-to-noise ratio. This work reports the generation of a flat, high power frequency comb in the telecom band using a 17 mm fully-integrated silicon core fibre as a parametric mixer. Our all-fibre, cavity-free source combines the material benefits of planar waveguide structures with the advantageous properties of fibre platforms to achieve a 30 nm bandwidth comb source containing 143 tones with <3 kHz linewidth, 12 dB flatness, and >30 dB OSNR over the entire spectral region.
Low-dimensional assemblies of metal-organic framework particles and mutually coordinated anisotropy
Authors: Lyu Dengping , Xu Wei , Payong Jae Elise L. , Zhang Tianran , Wang Yufeng 
Published: July 2022

AbstractAssembling metal-organic framework (MOF)-based particles is an emerging approach for creating colloidal superstructures and hierarchical functional materials. However, realization of this goal requires strategies that not only regulate particle interactions but also harness the anisotropic morphologies and functions of various frameworks. Here, by exploiting depletion interaction induced by ionic amphiphiles, we show the assembly of a broad range of low-dimensional MOF colloidal superstructures, including 1D straight chains, alternating or bundled chains, 2D films of hexagonal, square, centered rectangular, and snowflake-like architectures, and quasi-3D supercrystals. With well-defined polyhedral shapes, the MOF particles are mutually oriented upon assembly, producing super-frameworks with hierarchically coordinated crystallinity and micropores. We demonstrate this advantage by creating functional MOF films with optical anisotropy, in our cases, birefringence and anisotropic fluorescence. Given the variety of MOFs available, our technique should allow access to advanced materials for sensing, optics, and photonics.
Probing interlayer shear thermal deformation in atomically-thin van der Waals layered materials
Authors: Zhang Le , Wang Han , Zong Xinrong , Zhou Yongheng , Wang Taihong , Wang Lin , Chen Xiaolong 
Published: July 2022

AbstractAtomically-thin van der Waals layered materials, with both high in-plane stiffness and bending flexibility, offer a unique platform for thermomechanical engineering. However, the lack of effective characterization techniques hinders the development of this research topic. Here, we develop a direct experimental method and effective theoretical model to study the mechanical, thermal, and interlayer properties of van der Waals materials. This is accomplished by using a carefully designed WSe2-based heterostructure, where monolayer WSe2 serves as an in-situ strain meter. Combining experimental results and theoretical modelling, we are able to resolve the shear deformation and interlayer shear thermal deformation of each individual layer quantitatively in van der Waals materials. Our approach also provides important interlayer coupling information as well as key thermal parameters. The model can be applied to van der Waals materials with different layer numbers and various boundary conditions for both thermally-induced and mechanically-induced deformations.
Clinical characteristics and immune profile alterations in vaccinated individuals with breakthrough Delta SARS-CoV-2 infections
Authors: Fan Qinghong , Shi Jingrong , Yang Yanhong , Tang Guofang , Jiang Mengling , Li Jiaojiao , Tang Jingyan , Li Lu , Wen Xueliang , Zhang Lieguang , Deng Xizi , Wang Yaping , Lan Yun , Li Liya , Peng Ping , Tong Yuwei , Lu Huan , Yan Lili , Liu Ying , Cai Shuijiang , Li Yueping , Mo Xiaoneng , Li Meiyu , Deng Xilong , Hu Zhongwei , Yu Haisheng , Hu Fengyu , Liu Jinxin , Tang Xiaoping , Li Feng 
Published: July 2022

AbstractDespite timely immunization programs, and efficacious vaccines conveying protection against SARS-CoV-2 infection, breakthrough infections in vaccinated individuals have been reported. The Delta variant of concern (VOC) outbreak in Guangzhou resulted in local transmission in vaccinated and non-vaccinated residents, providing a unique opportunity to study the protective effects of the inactivated vaccines in breakthrough infection. Here, we find that the 2-dose vaccinated group has similar peak viral titers and comparable speeds of viral RNA clearance to the non-vaccinated group but accelerated viral suppression in the middle course of the disease. We quantitatively demonstrate that peak viral pneumonia is significantly mitigated in the 2-dose vaccine group (median 0.298%) compared with the non-vaccinated (5.77%) and 1-dose vaccine (3.34%) groups. Pneumonia absorbance is approximately 6 days ahead in the 2-dose group (median 10 days) than in the non-vaccinated group (16 days) (p = 0.003). We also observe reduced cytokine inflammation and markedly undisturbed gene transcription profiles of peripheral blood mononuclear cells (PBMCs) in the 2-dose group. In short, our study demonstrates that prior vaccination substantially restrains pneumonia development, reduces cytokine storms, and facilitates clinical recovery.
Precision digital mapping of endogenous and induced genomic DNA breaks by INDUCE-seq
Authors: Dobbs Felix M. , van Eijk Patrick , Fellows Mick D. , Loiacono Luisa , Nitsch Roberto , Reed Simon H. 
Published: July 2022

AbstractUnderstanding how breaks form and are repaired in the genome depends on the accurate measurement of the frequency and position of DNA double strand breaks (DSBs). This is crucial for identification of a chemical’s DNA damage potential and for safe development of therapies, including genome editing technologies. Current DSB sequencing methods suffer from high background levels, the inability to accurately measure low frequency endogenous breaks and high sequencing costs. Here we describe INDUCE-seq, which overcomes these problems, detecting simultaneously the presence of low-level endogenous DSBs caused by physiological processes, and higher-level recurrent breaks induced by restriction enzymes or CRISPR-Cas nucleases. INDUCE-seq exploits an innovative NGS flow cell enrichment method, permitting the digital detection of breaks. It can therefore be used to determine the mechanism of DSB repair and to facilitate safe development of therapeutic genome editing. We further discuss how the method can be adapted to detect other genomic features.
Compulsive alcohol drinking in rodents is associated with altered representations of behavioral control and seeking in dorsal medial prefrontal cortex
Authors: Timme Nicholas M. , Ma Baofeng , Linsenbardt David , Cornwell Ethan , Galbari Taylor , Lapish Christopher C. 
Published: July 2022

AbstractA key feature of compulsive alcohol drinking is continuing to drink despite negative consequences. To examine the changes in neural activity that underlie this behavior, compulsive alcohol drinking was assessed in a validated rodent model of heritable risk for excessive drinking (alcohol preferring (P) rats). Neural activity was measured in dorsal medial prefrontal cortex (dmPFC—a brain region involved in maladaptive decision-making) and assessed via change point analyses and novel principal component analyses. Neural population representations of specific decision-making variables were measured to determine how they were altered in animals that drink alcohol compulsively. Compulsive animals showed weakened representations of behavioral control signals, but strengthened representations of alcohol seeking-related signals. Finally, chemogenetic-based excitation of dmPFC prevented escalation of compulsive alcohol drinking. Collectively, these data indicate that compulsive alcohol drinking in rats is associated with alterations in dmPFC neural activity that underlie diminished behavioral control and enhanced seeking.
Interchromosomal interaction of homologous Stat92E alleles regulates transcriptional switch during stem-cell differentiation
Authors: Antel Matthew , Raj Romir , Masoud Madona Y. G. , Pan Ziwei , Li Sheng , Mellone Barbara G. , Inaba Mayu 
Published: July 2022

AbstractPairing of homologous chromosomes in somatic cells provides the opportunity of interchromosomal interaction between homologous gene regions. In the Drosophila male germline, the Stat92E gene is highly expressed in a germline stem cell (GSC) and gradually downregulated during the differentiation. Here we show that the pairing of Stat92E is always tight in GSCs and immediately loosened in differentiating daughter cells, gonialblasts (GBs). Disturbance of Stat92E pairing by relocation of one locus to another chromosome or by knockdown of global pairing/anti-pairing factors both result in a failure of Stat92E downregulation, suggesting that the pairing is required for the decline in transcription. Furthermore, the Stat92E enhancer, but not its transcription, is required for the change in pairing state, indicating that pairing is not a consequence of transcriptional changes. Finally, we show that the change in Stat92E pairing is dependent on asymmetric histone inheritance during the asymmetric division of GSCs. Taken together, we propose that the changes in Stat92E pairing status is an intrinsically programmed mechanism for enabling prompt cell fate switch during the differentiation of stem cells.
Chromatin sequesters pioneer transcription factor Sox2 from exerting force on DNA
Authors: Nguyen Tuan , Li Sai , Chang Jeremy T-H , Watters John W. , Ng Htet , Osunsade Adewola , David Yael , Liu Shixin 
Published: July 2022

AbstractBiomolecular condensation constitutes an emerging mechanism for transcriptional regulation. Recent studies suggest that the co-condensation between transcription factors (TFs) and DNA can generate mechanical forces driving genome rearrangements. However, the reported forces generated by protein-DNA co-condensation are typically below one piconewton (pN), questioning its physiological significance. Moreover, the force-generating capacity of these condensates in the chromatin context remains unknown. Here, we show that Sox2, a nucleosome-binding pioneer TF, forms co-condensates with DNA and generates forces up to 7 pN, exerting considerable mechanical tension on DNA strands. We find that the disordered domains of Sox2 are required for maximum force generation but not for condensate formation. Furthermore, we show that nucleosomes dramatically attenuate the mechanical stress exerted by Sox2 by sequestering it from coalescing on bare DNA. Our findings reveal that TF-mediated DNA condensation can exert significant mechanical stress on the genome which can nonetheless be attenuated by the chromatin architecture.
Programmable CRISPR-Cas9 microneedle patch for long-term capture and real-time monitoring of universal cell-free DNA
Authors: Yang Bin , Kong Jilie , Fang Xueen 
Published: July 2022

AbstractRecent advances in biointerfaces have led to the development of wearable devices that can provide insights into personal health. As wearable modules, microneedles can extract analytes of interest from interstitial fluid in a minimally invasive fashion. However, some microneedles are limited by their ability to perform highly effective extraction and real-time monitoring for macromolecule biomarkers simultaneously. Here we show the synergetic effect of CRISPR-activated graphene biointerfaces, and report an on-line wearable microneedle patch for extraction and in vivo long-term monitoring of universal cell-free DNA. In this study, this wearable system enables real-time monitoring of Epstein-Barr virus, sepsis, and kidney transplantation cell-free DNA, with anti-interference ability of 60% fetal bovine serum, and has satisfactory stable sensitivity for 10 days in vivo. The experimental results of immunodeficient mouse models shows the feasibility and practicability of this proposed method. This wearable patch holds great promise for long-term in vivo monitoring of cell-free DNA and could potentially be used for early disease screening and prognosis.
Ciliary transition zone proteins coordinate ciliary protein composition and ectosome shedding
Authors: Wang Liang , Wen Xin , Wang Zhengmao , Lin Zaisheng , Li Chunhong , Zhou Huilin , Yu Huimin , Li Yuhan , Cheng Yifei , Chen Yuling , Lou Geer , Pan Junmin , Cao Muqing 
Published: July 2022

AbstractThe transition zone (TZ) of the cilium/flagellum serves as a diffusion barrier that controls the entry/exit of ciliary proteins. Mutations of the TZ proteins disrupt barrier function and lead to multiple human diseases. However, the systematic regulation of ciliary composition and signaling-related processes by different TZ proteins is not completely understood. Here, we reveal that loss of TCTN1 inChlamydomonas reinhardtiidisrupts the assembly of wedge-shaped structures in the TZ. Proteomic analysis of cilia from WT and three TZ mutants,tctn1,cep290, andnphp4, shows a unique role of each TZ subunit in the regulation of ciliary composition, explaining the phenotypic diversity of different TZ mutants. Interestingly, we find that defects in the TZ impair the formation and biological activity of ciliary ectosomes. Collectively, our findings provide systematic insights into the regulation of ciliary composition by TZ proteins and reveal a link between the TZ and ciliary ectosomes.
Influence of flow regime on the decomposition of diluted methane in a nitrogen rotating gliding arc
Authors: J Ananthanarasimhan , Rao Lakshminarayana 
Published: July 2022

AbstractThis work reports the operation of rotating gliding arc (RGA) reactor at a high flow rate and the effect of flow regimes on its chemical performance, which is not explored much. When the flow regime was changed from transitional to turbulent flow ($$5\rightarrow 50~\hbox {SLPM}$$

5
→
50

SLPM

), operation mode transitioned from glow to spark type; the average electric field, gas temperature, and electron temperature raised ($$106\rightarrow 156~\hbox {V}\cdot \hbox {mm}^{-1}$$

106
→
156

V
·

mm

-
1

, $$3681\rightarrow 3911~\hbox {K}$$

3681
→
3911

K

, and $$1.62\rightarrow 2.12~\hbox {eV}$$

1.62
→
2.12

eV

). The decomposition’s energy efficiency ($$\eta _E$$

η
E

) increased by a factor of 3.9 ($$16.1\rightarrow 61.9~\hbox {g}_{{\text{CH}}_{4}}\cdot \hbox {kWh}^{-1}$$

16.1
→
61.9

g

CH
4

·

kWh

-
1

). The first three dominant methane consumption reactions (MCR) for both the flow regimes were induced by $$\text {H}$$
H
, CH, and $$\text {CH}_3$$

CH
3

(key-species), yet differed by their contribution values. The MCR rate increased by 80–148% [induced by e and singlet—$$\text {N}_2$$

N
2

], and decreased by 34–93% [CH, $$\text {CH}_3$$

CH
3

, triplet—$$\text {N}_2$$

N
2

], due to turbulence. The electron-impact processes generated atleast 50% more of key-species and metastables for every 100 eV of input energy, explaining the increased $$\eta _E$$

η
E

at turbulent flow. So, flow regime influences the plasma chemistry and characteristics through flow rate. The reported RGA reactor is promising to mitigate the fugitive hydrocarbon emissions energy efficiently at a large scale, requiring some optimization to improve conversion.