bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cancer-specific tissue-resident memory T-cells express ZNF683 in colorectal cancer
Authors: Kitakaze Masatoshi , Uemura Mamoru , Hara Tomoaki , Chijimatsu Ryota , Motooka Daisuke , Hirai Toshiro , Konno Masamitsu , Okuzaki Daisuke , Sekido Yuki , Hata Tsuyoshi , Ogino Takayuki , Takahashi Hidekazu , Miyoshi Norikatsu , Ofusa Ken , Mizushima Tsunekazu , Eguchi Hidetoshi , Doki Yuichiro , Ishii Hideshi 
Published: March 2023

Abstract
Background
Tissue-resident memory T (Trm) cells are associated with cytotoxicity not only in viral infection and autoimmune disease pathologies but also in many cancers. Tumour-infiltrating CD103+ Trm cells predominantly comprise CD8 T cells that express cytotoxic activation and immune checkpoint molecules called exhausted markers. This study aimed to investigate the role of Trm in colorectal cancer (CRC) and characterise the cancer-specific Trm.

Methods
Immunochemical staining with anti-CD8 and anti-CD103 antibodies for resected CRC tissues was used to identify the tumour-infiltrating Trm cells. The Kaplan–Meier estimator was used to evaluate the prognostic significance. Cells immune to CRC were targeted for single-cell RNA-seq analysis to characterise cancer-specific Trm cells in CRC.

Results
The number of CD103+/CD8+ tumour-infiltrating lymphocytes (TILs) was a favourable prognostic and predictive factor of the overall survival and recurrence-free survival in patients with CRC. Single-cell RNA-seq analysis of 17,257 CRC-infiltrating immune cells revealed a more increased zinc finger protein 683 (ZNF683) expression in cancer Trm cells than in noncancer Trm cells and in high-infiltrating Trm cells than low-infiltrating Trm in cancer, with an upregulated T-cell receptor (TCR)- and interferon-γ (IFN-γ) signalling-related gene expression in ZNF683+ Trm cells.

Conclusions
The number of CD103+/CD8+ TILs is a prognostic predictive factor in CRC. In addition, we identified the ZNF683 expression as one of the candidate markers of cancer-specific Trm cells. IFN-γ and TCR signalling and ZNF683 expression are involved in Trm cell activation in tumours and are promising targets for cancer immunity regulation.
RNA splicing analysis using heterogeneous and large RNA-seq datasets
Authors: Vaquero-Garcia Jorge , Aicher Joseph K. , Jewell San , Gazzara Matthew R. , Radens Caleb M. , Jha Anupama , Norton Scott S. , Lahens Nicholas F. , Grant Gregory R. , Barash Yoseph 
Published: March 2023

AbstractThe ubiquity of RNA-seq has led to many methods that use RNA-seq data to analyze variations in RNA splicing. However, available methods are not well suited for handling heterogeneous and large datasets. Such datasets scale to thousands of samples across dozens of experimental conditions, exhibit increased variability compared to biological replicates, and involve thousands of unannotated splice variants resulting in increased transcriptome complexity. We describe here a suite of algorithms and tools implemented in the MAJIQ v2 package to address challenges in detection, quantification, and visualization of splicing variations from such datasets. Using both large scale synthetic data and GTEx v8 as benchmark datasets, we assess the advantages of MAJIQ v2 compared to existing methods. We then apply MAJIQ v2 package to analyze differential splicing across 2,335 samples from 13 brain subregions, demonstrating its ability to offer insights into brain subregion-specific splicing regulation.
Fibroblastic reticular cells in lymph node potentiate white adipose tissue beiging through neuro-immune crosstalk in male mice
Authors: Cheong Lai Yee , Wang Baile , Wang Qin , Jin Leigang , Kwok Kelvin H. M. , Wu Xiaoping , Shu Lingling , Lin Huige , Chung Sookja Kim , Cheng Kenneth K. Y. , Hoo Ruby L. C. , Xu Aimin 
Published: March 2023

AbstractLymph nodes (LNs) are always embedded in the metabolically-active white adipose tissue (WAT), whereas their functional relationship remains obscure. Here, we identify fibroblastic reticular cells (FRCs) in inguinal LNs (iLNs) as a major source of IL-33 in mediating cold-induced beiging and thermogenesis of subcutaneous WAT (scWAT). Depletion of iLNs in male mice results in defective cold-induced beiging of scWAT. Mechanistically, cold-enhanced sympathetic outflow to iLNs activates β1- and β2-adrenergic receptor (AR) signaling in FRCs to facilitate IL-33 release into iLN-surrounding scWAT, where IL-33 activates type 2 immune response to potentiate biogenesis of beige adipocytes. Cold-induced beiging of scWAT is abrogated by selective ablation of IL-33 or β1- and β2-AR in FRCs, or sympathetic denervation of iLNs, whereas replenishment of IL-33 reverses the impaired cold-induced beiging in iLN-deficient mice. Taken together, our study uncovers an unexpected role of FRCs in iLNs in mediating neuro-immune interaction to maintain energy homeostasis.
Site-specific anisotropic assembly of amorphous mesoporous subunits on crystalline metal–organic framework
Authors: Liu Minchao , Shang Cheng , Zhao Tiancong , Yu Hongyue , Kou Yufang , Lv Zirui , Hou Mengmeng , Zhang Fan , Li Qiaowei , Zhao Dongyuan , Li Xiaomin 
Published: March 2023

AbstractAs an important branch of anisotropic nanohybrids (ANHs) with multiple surfaces and functions, the porous ANHs (p-ANHs) have attracted extensive attentions because of the unique characteristics of high surface area, tunable pore structures and controllable framework compositions, etc. However, due to the large surface-chemistry and lattice mismatches between the crystalline and amorphous porous nanomaterials, the site-specific anisotropic assembly of amorphous subunits on crystalline host is challenging. Here, we report a selective occupation strategy to achieve site-specific anisotropic growth of amorphous mesoporous subunits on crystalline metal–organic framework (MOF). The amorphous polydopamine (mPDA) building blocks can be controllably grown on the {100} (type 1) or {110} (type 2) facets of crystalline ZIF-8 to form the binary super-structured p-ANHs. Based on the secondary epitaxial growth of tertiary MOF building blocks on type 1 and 2 nanostructures, the ternary p-ANHs with controllable compositions and architectures are also rationally synthesized (type 3 and 4). These intricate and unprecedented superstructures provide a good platform for the construction of nanocomposites with multiple functionalities and understanding of the structure-property-function relationships.
ARF suppression by MYC but not MYCN confers increased malignancy of aggressive pediatric brain tumors
Authors: Mainwaring Oliver J. , Weishaupt Holger , Zhao Miao , Rosén Gabriela , Borgenvik Anna , Breinschmid Laura , Verbaan Annemieke D. , Richardson Stacey , Thompson Dean , Clifford Steven C. , Hill Rebecca M. , Annusver Karl , Sundström Anders , Holmberg Karl O. , Kasper Maria , Hutter Sonja , Swartling Fredrik J. 
Published: March 2023

AbstractMedulloblastoma, the most common malignant pediatric brain tumor, often harbors MYC amplifications. Compared to high-grade gliomas, MYC-amplified medulloblastomas often show increased photoreceptor activity and arise in the presence of a functional ARF/p53 suppressor pathway. Here, we generate an immunocompetent transgenic mouse model with regulatable MYC that develop clonal tumors that molecularly resemble photoreceptor-positive Group 3 medulloblastoma. Compared to MYCN-expressing brain tumors driven from the same promoter, pronounced ARF silencing is present in our MYC-expressing model and in human medulloblastoma. While partial Arf suppression causes increased malignancy in MYCN-expressing tumors, complete Arf depletion promotes photoreceptor-negative high-grade glioma formation. Computational models and clinical data further identify drugs targeting MYC-driven tumors with a suppressed but functional ARF pathway. We show that the HSP90 inhibitor, Onalespib, significantly targets MYC-driven but not MYCN-driven tumors in an ARF-dependent manner. The treatment increases cell death in synergy with cisplatin and demonstrates potential for targeting MYC-driven medulloblastoma.
Genetic requirements for repair of lesions caused by single genomic ribonucleotides in S phase
Authors: Schindler Natalie , Tonn Matthias , Kellner Vanessa , Fung Jia Jun , Lockhart Arianna , Vydzhak Olga , Juretschke Thomas , Möckel Stefanie , Beli Petra , Khmelinskii Anton , Luke Brian 
Published: March 2023

AbstractSingle ribonucleoside monophosphates (rNMPs) are transiently present in eukaryotic genomes. The RNase H2-dependent ribonucleotide excision repair (RER) pathway ensures error-free rNMP removal. In some pathological conditions, rNMP removal is impaired. If these rNMPs hydrolyze during, or prior to, S phase, toxic single-ended double-strand breaks (seDSBs) can occur upon an encounter with replication forks. How such rNMP-derived seDSB lesions are repaired is unclear. We expressed a cell cycle phase restricted allele of RNase H2 to nick at rNMPs in S phase and study their repair. Although Top1 is dispensable, the RAD52 epistasis group and Rtt101Mms1-Mms22 dependent ubiquitylation of histone H3 become essential for rNMP-derived lesion tolerance. Consistently, loss of Rtt101Mms1-Mms22 combined with RNase H2 dysfunction leads to compromised cellular fitness. We refer to this repair pathway as nick lesion repair (NLR). The NLR genetic network may have important implications in the context of human pathologies.
An autoimmune pleiotropic SNP modulates IRF5 alternative promoter usage through ZBTB3-mediated chromatin looping
Authors: Wang Zhao , Liang Qian , Qian Xinyi , Hu Bolang , Zheng Zhanye , Wang Jianhua , Hu Yuelin , Bao Zhengkai , Zhao Ke , Zhou Yao , Feng Xiangling , Yi Xianfu , Li Jin , Shi Jiandang , Liu Zhe , Hao Jihui , Chen Kexin , Yu Ying , Sham Pak Chung , Lu Wange , Wang Xiaoyan , Song Weihong , Li Mulin Jun 
Published: March 2023

AbstractGenetic sharing is extensively observed for autoimmune diseases, but the causal variants and their underlying molecular mechanisms remain largely unknown. Through systematic investigation of autoimmune disease pleiotropic loci, we found most of these shared genetic effects are transmitted from regulatory code. We used an evidence-based strategy to functionally prioritize causal pleiotropic variants and identify their target genes. A top-ranked pleiotropic variant, rs4728142, yielded many lines of evidence as being causal. Mechanistically, the rs4728142-containing region interacts with the IRF5 alternative promoter in an allele-specific manner and orchestrates its upstream enhancer to regulate IRF5 alternative promoter usage through chromatin looping. A putative structural regulator, ZBTB3, mediates the allele-specific loop to promote IRF5-short transcript expression at the rs4728142 risk allele, resulting in IRF5 overactivation and M1 macrophage polarization. Together, our findings establish a causal mechanism between the regulatory variant and fine-scale molecular phenotype underlying the dysfunction of pleiotropic genes in human autoimmunity.
Return of the Tbx5; lineage-tracing reveals ventricular cardiomyocyte-like precursors in the injured adult mammalian heart
Authors: Siatra Panagiota , Vatsellas Giannis , Chatzianastasiou Athanasia , Balafas Evangelos , Manolakou Theodora , Papapetropoulos Andreas , Agapaki Anna , Mouchtouri Eleni-Taxiarchia , Ruchaya Prashant J. , Korovesi Artemis G. , Mavroidis Manolis , Thanos Dimitrios , Beis Dimitris , Kokkinopoulos Ioannis 
Published: March 2023

AbstractThe single curative measure for heart failure patients is a heart transplantation, which is limited due to a shortage of donors, the need for immunosuppression and economic costs. Therefore, there is an urgent unmet need for identifying cell populations capable of cardiac regeneration that we will be able to trace and monitor. Injury to the adult mammalian cardiac muscle, often leads to a heart attack through the irreversible loss of a large number of cardiomyocytes, due to an idle regenerative capability. Recent reports in zebrafish indicate that Tbx5a is a vital transcription factor for cardiomyocyte regeneration. Preclinical data underscore the cardioprotective role of Tbx5 upon heart failure. Data from our earlier murine developmental studies have identified a prominent unipotent Tbx5-expressing embryonic cardiac precursor cell population able to form cardiomyocytes, in vivo, in vitro and ex vivo. Using a developmental approach to an adult heart injury model and by employing a lineage-tracing mouse model as well as the use of single-cell RNA-seq technology, we identify a Tbx5-expressing ventricular cardiomyocyte-like precursor population, in the injured adult mammalian heart. The transcriptional profile of that precursor cell population is closer to that of neonatal than embryonic cardiomyocyte precursors. Tbx5, a cardinal cardiac development transcription factor, lies in the center of a ventricular adult precursor cell population, which seems to be affected by neurohormonal spatiotemporal cues. The identification of a Tbx5-specific cardiomyocyte precursor-like cell population, which is capable of dedifferentiating and potentially deploying a cardiomyocyte regenerative program, provides a clear target cell population for translationally-relevant heart interventional studies.
Human exposure to per- and polyfluoroalkyl substances and other emerging contaminants in drinking water
Authors: Cserbik Dora , Redondo-Hasselerharm Paula E. , Farré Maria J. , Sanchís Josep , Bartolomé Arantxa , Paraian Alexandra , Herrera Eva María , Caixach Josep , Villanueva Cristina M. , Flores Cintia 
Published: March 2023

AbstractA wide range of chemicals was measured in different types of drinking water and urine samples through target and non-target screening (NTS) to estimate human exposure. Tap water samples collected from 42 locations in Barcelona (August–October/2020, May/2021), tap water filtered with domestic activated carbon filters (AC, N = 6) and reverse osmosis (RO, N = 5), commercial bottled water (N = 10), and urine (N = 39) samples were included. 35 per- and polyfluoroalkyl substances (PFAS), bisphenol A, and nonylphenol were analyzed using LC–MS/MS and GC–MS/MS, and NTS using LC–HRMS. 9 PFAS were detected in unfiltered tap water of first sampling (79% samples, median = 30 ng/L), 6 in the second (69%, median = 9.8 ng/L), and 5 in 13% urine samples. NTS tentatively identified pharmaceuticals and other industrial chemicals in drinking water. PFAS were removed by RO and not by AC filters. Findings provide valuable information for exposure science and water quality monitoring of emerging drinking water contaminants.
Sand fly population dynamics in areas of American cutaneous leishmaniasis, Municipality of Paraty, Rio de Janeiro, Brazil
Authors: Vieira Vanessa Rendeiro , de Aguiar Gustavo Marins , de Azevedo Alfredo Carlos Rodrigues , Rangel Elizabeth Ferreira , Guimarães Anthony Érico 
Published: March 2023

AbstractThe present study is the second and last part of the study that investigated the fauna and behavior of sand flies in areas prone to cutaneous leishmaniasis outbreaks, in the State of Rio de Janeiro, in the municipality of Paraty. To collect the sand flies, CDC and Shannon light traps were used, installed in the peridomiciliary and forest areas, and manual suction tubes on the walls of the home and in the animal shelters. A total of 102,937 sand flies, belonging to nine genera and 23 species were captured from October 2009 to September 2012. Regarding the monthly frequency of sand flies, the period of highest density was from November to March, with a maximum peak in January. The lowest density was observed in June and July. In the studied area, the species of epidemiological importance, Nyssomyia intermedia, Pintomyia fischeri, Migonemyia migonei and Nyssomyia whitmani, were found in all months of the year, a period in which residents may be in contact with these vectors of the etiological agent of cutaneous leishmaniasis.
Full C-band wavelength-tunable, 250 MHz repetition rate mode-locked polarization-maintaining fiber laser
Authors: Jang Yoon-Soo , Park Jungjae , Jin Jonghan 
Published: March 2023

AbstractWe demonstrate a full C-band wavelength-tunable mode-locked fiber laser with a repetition rate of 250 MHz, representing the highest repetition rate for C-band tunable mode-locked lasers thus far to the best of our knowledge. The polarization-maintaining fiber-based Fabry–Perot cavity enables a fundamental repetition rate of 250 MHz with a semiconductor saturable absorber mirror as a mode-locker. We observed a stable and single soliton mode-locking state with wide tunability of the center wavelength from 1505 to 1561 nm by adjusting the incident angle of a bandpass filter inside the cavity. The wavelength-tunable high-repetition-rate mode-locked laser covering the full C-band is expected to be a compelling source for many frequency-comb-based applications, including high-precision optical metrology, broadband absorption spectroscopy, and broadband optical frequency synthesizers.
Genomic characteristics and clinical significance of CD56+ circulating tumor cells in small cell lung cancer
Authors: Ricordel Charles , Chaillot L. , Vlachavas E. I. , Logotheti M. , Jouannic A. , Desvallees T. , Lecuyer G. , Aubry M. , Kontogianni G. , Mastrokalou C. , Jouan F. , Jarry U. , Corre R. , Le Guen Y. , Guillaudeux T. , Lena H. , Chatziioannou A. , Pedeux Rémy 
Published: March 2023

AbstractCirculating tumor cells (CTC) have been studied in various solid tumors but clinical utility of CTC in small cell lung cancer (SCLC) remains unclear. The aim of the CTC-CPC study was to develop an EpCAM-independent CTC isolation method allowing isolation of a broader range of living CTC from SCLC and decipher their genomic and biological characteristics. CTC-CPC is a monocentric prospective non-interventional study including treatment-naïve newly diagnosed SCLC. CD56+ CTC were isolated from whole blood samples, at diagnosis and relapse after first-line treatment and submitted to whole-exome-sequencing (WES). Phenotypic study confirms tumor lineage and tumorigenic properties of isolated cells for the 4 patients analyzed with WES. WES of CD56+ CTC and matched tumor biopsy reveal genomic alteration frequently impaired in SCLC. At diagnosis CD56+ CTC were characterized by a high mutation load, a distinct mutational profile and a unique genomic signature, compared to match tumors biopsies. In addition to classical pathways altered in SCLC, we found new biological processes specifically affected in CD56+ CTC at diagnosis. High numeration of CD56+ CTC (> 7/ml) at diagnosis was associated with ES-SCLC. Comparing CD56+ CTC isolated at diagnosis and relapse, we identify differentially altered oncogenic pathways (e.g. DLL3 or MAPK pathway). We report a versatile method of CD56+ CTC detection in SCLC. Numeration of CD56+ CTC at diagnosis is correlated with disease extension. Isolated CD56+ CTC are tumorigenic and show a distinct mutational profile. We report a minimal gene set as a unique signature of CD56+ CTC and identify new affected biological pathways enriched in EpCAM-independent isolated CTC in SCLC.
Observational evidence of salt finger in the diurnal thermocline
Authors: Ashin K. , Girishkumar M. S. , D’Asaro Eric , Jofia J. , Sherin V. R. , Sureshkumar N. , Rao E. Pattabhi Ram 
Published: March 2023

AbstractDue to strong turbulent mixing, the ocean surface boundary layer region is generally not conducive to double diffusion. However, vertical microstructure profiles observations in the northeastern Arabian Sea during May 2019 imply the formation of salt fingers in the diurnal thermocline (DT) region during the daytime. In the DT layer, conditions are favorable for salt fingering: Turner angle values are between 50 and 55° with both temperature and salinity decreasing with depth; shear-driven mixing is weak with a turbulent Reynolds number of about 30. The presence of salt fingering in the DT is confirmed by the presence of staircase-like structures with step sizes larger than the Ozmidov length and by the dissipation ratio that is larger than the mixing coefficient. The unusual daytime salinity maximum in the mixed layer that supports salt fingering is primarily due to a daytime reduction in vertical entrainment of fresh water along with minor contributions from evaporation and horizontal advection and a significant contribution from detrainment processes.
Microbiomes of a disease-resistant genotype of Acropora cervicornis are resistant to acute, but not chronic, nutrient enrichment
Authors: Klinges J. Grace , Patel Shalvi H. , Duke William C. , Muller Erinn M. , Vega Thurber Rebecca L. 
Published: March 2023

AbstractChronically high levels of inorganic nutrients have been documented in Florida’s coral reefs and are linked to increased prevalence and severity of coral bleaching and disease. Naturally disease-resistant genotypes of the staghorn coral Acropora cervicornis are rare, and it is unknown whether prolonged exposure to acute or chronic high nutrient levels will reduce the disease tolerance of these genotypes. Recently, the relative abundance of the bacterial genus Aquarickettsia was identified as a significant indicator of disease susceptibility in A. cervicornis, and the abundance of this bacterial species was previously found to increase under chronic and acute nutrient enrichment. We therefore examined the impact of common constituents of nutrient pollution (phosphate, nitrate, and ammonium) on microbial community structure in a disease-resistant genotype with naturally low abundances of Aquarickettsia. We found that although this putative parasite responded positively to nutrient enrichment in a disease-resistant host, relative abundances remained low (< 0.5%). Further, while microbial diversity was not altered significantly after 3 weeks of nutrient enrichment, 6 weeks of enrichment was sufficient to shift microbiome diversity and composition. Coral growth rates were also reduced by 6 weeks of nitrate treatment compared to untreated conditions. Together these data suggest that the microbiomes of disease-resistant A. cervicornis may be initially resistant to shifts in microbial community structure, but succumb to compositional and diversity alterations after more sustained environmental pressure. As the maintenance of disease-resistant genotypes is critical for coral population management and restoration, a complete understanding of how these genotypes respond to environmental stressors is necessary to predict their longevity.