bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sulfoquinovose is a widespread organosulfur substrate for Roseobacter clade bacteria in the ocean
Authors: Liu Le , Chen Xiaofeng , Ye Jianing , Ma Xiaoyi , Han Yu , He Yajie , Tang Kai 
Published: January 2023

Abstract
Sulfoquinovose (SQ) is one of the most abundant organosulfur compounds in the biosphere, and its biosynthesis and degradation can represent an important contribution to the sulfur cycle. To data, in marine environments, the microorganisms capable of metabolising SQ have remained unidentified and the sources of SQ are still uncertain. Herein, the marine Roseobacter clade bacteria (RCB) Dinoroseobacter shibae DFL 12 and Roseobacter denitrificans OCh 114 were found to grow using SQ as the sole source of carbon and energy. In the presence of SQ, we identified a set of highly up-regulated proteins encoded by gene clusters in these two organisms, of which four homologues to proteins in the SQ monooxygenase pathway of Agrobacterium fabrum C58 may confer the ability to metabolise SQ to these marine bacteria. The sulfite released from SQ desulfonation by FMN-dependent SQ monooxygenase (SmoC) may provide bacteria with reduced sulfur for assimilation, while proteins associated with sulfite production via assimilatory sulfate reduction were significantly down-regulated. Such SQ catabolic genes are restricted to a limited number of phylogenetically diverse bacterial taxa with the predominate genera belonging to the Roseobacter clade (Roseobacteraceae). Moreover, transcript analysis of Tara Oceans project and coastal Bohai Sea samples provided additional evidence for SQ metabolism by RCB. SQ was found to be widely distributed in marine phytoplankton and cyanobacteria with variable intracellular concentrations ranging from micromolar to millimolar levels, and the amounts of SQ on particulate organic matter in field samples were, on average, lower than that of dimethylsulfoniopropionate (DMSP) by one order of magnitude. Together, the phototroph-derived SQ actively metabolised by RCB represents a previously unidentified link in the marine sulfur cycle.
The role of TGF-beta3 in cartilage development and osteoarthritis
Authors: Du Xinmei , Cai Linyi , Xie Jing , Zhou Xuedong 
Published: January 2023

AbstractArticular cartilage serves as a low-friction, load-bearing tissue without the support with blood vessels, lymphatics and nerves, making its repair a big challenge. Transforming growth factor-beta 3 (TGF-β3), a vital member of the highly conserved TGF-β superfamily, plays a versatile role in cartilage physiology and pathology. TGF-β3 influences the whole life cycle of chondrocytes and mediates a series of cellular responses, including cell survival, proliferation, migration, and differentiation. Since TGF-β3 is involved in maintaining the balance between chondrogenic differentiation and chondrocyte hypertrophy, its regulatory role is especially important to cartilage development. Increased TGF-β3 plays a dual role: in healthy tissues, it can facilitate chondrocyte viability, but in osteoarthritic chondrocytes, it can accelerate the progression of disease. Recently, TGF-β3 has been recognized as a potential therapeutic target for osteoarthritis (OA) owing to its protective effect, which it confers by enhancing the recruitment of autologous mesenchymal stem cells (MSCs) to damaged cartilage. However, the biological mechanism of TGF-β3 action in cartilage development and OA is not well understood. In this review, we systematically summarize recent progress in the research on TGF-β3 in cartilage physiology and pathology, providing up-to-date strategies for cartilage repair and preventive treatment.
Inhibition of fibroblast activation protein ameliorates cartilage matrix degradation and osteoarthritis progression
Authors: Fan Aoyuan , Wu Genbin , Wang Jianfang , Lu Laiya , Wang Jingyi , Wei Hanjing , Sun Yuxi , Xu Yanhua , Mo Chunyang , Zhang Xiaoying , Pang Zhiying , Pan Zhangyi , Wang Yiming , Lu Liangyu , Fu Guojian , Ma Mengqiu , Zhu Qiaoling , Cao Dandan , Qin Jiachen , Yin Feng , Yue Rui 
Published: January 2023

AbstractFibroblast activation protein (Fap) is a serine protease that degrades denatured type I collagen, α2-antiplasmin and FGF21. Fap is highly expressed in bone marrow stromal cells and functions as an osteogenic suppressor and can be inhibited by the bone growth factor Osteolectin (Oln). Fap is also expressed in synovial fibroblasts and positively correlated with the severity of rheumatoid arthritis (RA). However, whether Fap plays a critical role in osteoarthritis (OA) remains poorly understood. Here, we found that Fap is significantly elevated in osteoarthritic synovium, while the genetic deletion or pharmacological inhibition of Fap significantly ameliorated posttraumatic OA in mice. Mechanistically, we found that Fap degrades denatured type II collagen (Col II) and Mmp13-cleaved native Col II. Intra-articular injection of rFap significantly accelerated Col II degradation and OA progression. In contrast, Oln is expressed in the superficial layer of articular cartilage and is significantly downregulated in OA. Genetic deletion of Oln significantly exacerbated OA progression, which was partially rescued by Fap deletion or inhibition. Intra-articular injection of rOln significantly ameliorated OA progression. Taken together, these findings identify Fap as a critical pathogenic factor in OA that could be targeted by both synthetic and endogenous inhibitors to ameliorate articular cartilage degradation.
Co-targeting BCL-XL and MCL-1 with DT2216 and AZD8055 synergistically inhibit small-cell lung cancer growth without causing on-target toxicities in mice
Authors: Khan Sajid , Kellish Patrick , Connis Nick , Thummuri Dinesh , Wiegand Janet , Zhang Peiyi , Zhang Xuan , Budamagunta Vivekananda , Hua Nan , Yang Yang , De Umasankar , Jin Lingtao , Zhang Weizhou , Zheng Guangrong , Hromas Robert , Hann Christine , Zajac-Kaye Maria , Kaye Frederic J. , Zhou Daohong 
Published: January 2023

AbstractSmall-cell lung cancer (SCLC) is an aggressive malignancy with limited therapeutic options. The dismal prognosis in SCLC is in part associated with an upregulation of BCL-2 family anti-apoptotic proteins, including BCL-XL and MCL-1. Unfortunately, the currently available inhibitors of BCL-2 family anti-apoptotic proteins, except BCL-2 inhibitors, are not clinically relevant because of various on-target toxicities. We, therefore, aimed to develop an effective and safe strategy targeting these anti-apoptotic proteins with DT2216 (our platelet-sparing BCL-XL degrader) and AZD8055 (an mTOR inhibitor) to avoid associated on-target toxicities while synergistically optimizing tumor response. Through BH3 mimetic screening, we identified a subset of SCLC cell lines that is co-dependent on BCL-XL and MCL-1. After screening inhibitors of selected tumorigenic pathways, we found that AZD8055 selectively downregulates MCL-1 in SCLC cells and its combination with DT2216 synergistically killed BCL-XL/MCL-1 co-dependent SCLC cells, but not normal cells. Mechanistically, the combination caused BCL-XL degradation and suppression of MCL-1 expression, and thus disrupted MCL-1 interaction with BIM leading to an enhanced apoptotic induction. In vivo, the DT2216 + AZD8055 combination significantly inhibited the growth of cell line-derived and patient-derived xenografts and reduced tumor burden accompanied by increased survival in a genetically engineered mouse model of SCLC without causing appreciable thrombocytopenia or other normal tissue injuries. Thus, these preclinical findings lay a strong foundation for future clinical studies to test DT2216 + mTOR inhibitor combinations in a subset of SCLC patients whose tumors are co-driven by BCL-XL and MCL-1.
RALF signaling pathway activates MLO calcium channels to maintain pollen tube integrity
Authors: Gao Qifei , Wang Chao , Xi Yasheng , Shao Qiaolin , Hou Congcong , Li Legong , Luan Sheng 
Published: January 2023

AbstractPollen tube tip growth requires intricate Ca2+ signaling. Recent studies have also identified rapid alkalization factor (RALF)-family peptides and their receptors as critical components for pollen tube tip growth and integrity. The functional relationship of RALF and calcium signaling modules remains largely unclear. Here we report that disruption of RALF signaling pathway abolished the cytosolic Ca2+ gradient in the pollen tube, indicating that Ca2+ signaling is downstream of the RALF signaling pathway. We identified MILDEW RESISTANCE LOCUS O (MLO) family proteins MLO1, 5, 9, 15, as Ca2+ channels required for Ca2+ influx and pollen tube integrity. We further reconstituted the biochemical pathway in which signaling via RALF and RALF receptors activated MLO1/5/9/15 calcium channels. Together, we conclude that RALF peptides derived from pollen tube bind to their receptors to establish pollen tube Ca2+ gradient through activation of the MLO channels. Our finding has thus provided a mechanistic link between the RALF signaling pathway and Ca2+ signaling in controlling pollen tube integrity and growth.
De novo genes with an lncRNA origin encode unique human brain developmental functionality
Authors: An Ni A. , Zhang Jie , Mo Fan , Luan Xuke , Tian Lu , Shen Qing Sunny , Li Xiangshang , Li Chunqiong , Zhou Fanqi , Zhang Boya , Ji Mingjun , Qi Jianhuan , Zhou Wei-Zhen , Ding Wanqiu , Chen Jia-Yu , Yu Jia , Zhang Li , Shu Shaokun , Hu Baoyang , Li Chuan-Yun 
Published: January 2023

AbstractHuman de novo genes can originate from neutral long non-coding RNA (lncRNA) loci and are evolutionarily significant in general, yet how and why this all-or-nothing transition to functionality happens remains unclear. Here, in 74 human/hominoid-specific de novo genes, we identified distinctive U1 elements and RNA splice-related sequences accounting for RNA nuclear export, differentiating mRNAs from lncRNAs, and driving the origin of de novo genes from lncRNA loci. The polymorphic sites facilitating the lncRNA–mRNA conversion through regulating nuclear export are selectively constrained, maintaining a boundary that differentiates mRNAs from lncRNAs. The functional new genes actively passing through it thus showed a mode of pre-adaptive origin, in that they acquire functions along with the achievement of their coding potential. As a proof of concept, we verified the regulations of splicing and U1 recognition on the nuclear export efficiency of one of these genes, the ENSG00000205704, in human neural progenitor cells. Notably, knock-out or over-expression of this gene in human embryonic stem cells accelerates or delays the neuronal maturation of cortical organoids, respectively. The transgenic mice with ectopically expressed ENSG00000205704 showed enlarged brains with cortical expansion. We thus demonstrate the key roles of nuclear export in de novo gene origin. These newly originated genes should reflect the novel uniqueness of human brain development.
Protection of cell therapeutics from antibody-mediated killing by CD64 overexpression
Authors: Gravina Alessia , Tediashvili Grigol , Rajalingam Raja , Quandt Zoe , Deisenroth Chad , Schrepfer Sonja , Deuse Tobias 
Published: January 2023

AbstractAllogeneic cell therapeutics for cancer therapy or regenerative medicine are susceptible to antibody-mediated killing, which diminishes their efficacy. Here we report a strategy to protect cells from antibody-mediated killing that relies on engineered overexpression of the IgG receptor CD64. We show that human and mouse iPSC-derived endothelial cells (iECs) overexpressing CD64 escape antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity from IgG antibodies in vitro and in ADCC-enabled mice. When CD64 expression was combined with hypoimmune genetic modifications known to protect against cellular immunity, B2M−/−CIITA−/− CD47/CD64-transgenic iECs were resistant to both IgG antibody-mediated and cellular immune killing in vitro and in humanized mice. Mechanistic studies demonstrated that CD64 or its intracellularly truncated analog CD64t effectively capture monomeric IgG and occupy their Fc, and the IgG bind and occupy their target antigens. In three applications of the approach, human CD64t-engineered thyroid epithelial cells, pancreatic beta cells and CAR T cells withstood clinically relevant levels of graft-directed antibodies and fully evaded antibody-mediated killing.
Identification of patient-specific CD4+ and CD8+ T cell neoantigens through HLA-unbiased genetic screens
Authors: Cattaneo Chiara M. , Battaglia Thomas , Urbanus Jos , Moravec Ziva , Voogd Rhianne , de Groot Rosa , Hartemink Koen J. , Haanen John B. A. G. , Voest Emile E. , Schumacher Ton N. , Scheper Wouter 
Published: January 2023

AbstractCancer neoantigens that arise from tumor mutations are drivers of tumor-specific T cell responses, but identification of T cell-recognized neoantigens in individual patients is challenging. Previous methods have restricted antigen discovery to selected HLA alleles, thereby limiting the breadth of neoantigen repertoires that can be uncovered. Here, we develop a genetic neoantigen screening system that allows sensitive identification of CD4+ and CD8+ T cell-recognized neoantigens across patients’ complete HLA genotypes.
Accurate isoform discovery with IsoQuant using long reads
Authors: Prjibelski Andrey D. , Mikheenko Alla , Joglekar Anoushka , Smetanin Alexander , Jarroux Julien , Lapidus Alla L. , Tilgner Hagen U. 
Published: January 2023

AbstractAnnotating newly sequenced genomes and determining alternative isoforms from long-read RNA data are complex and incompletely solved problems. Here we present IsoQuant—a computational tool using intron graphs that accurately reconstructs transcripts both with and without reference genome annotation. For novel transcript discovery, IsoQuant reduces the false-positive rate fivefold and 2.5-fold for Oxford Nanopore reference-based or reference-free mode, respectively. IsoQuant also improves performance for Pacific Biosciences data.
Real-time, volumetric imaging of radiation dose delivery deep into the liver during cancer treatment
Authors: Zhang Wei , Oraiqat Ibrahim , Litzenberg Dale , Chang Kai-Wei , Hadley Scott , Sunbul Noora Ba , Matuszak Martha M. , Tichacek Christopher J. , Moros Eduardo G. , Carson Paul L. , Cuneo Kyle C. , Wang Xueding , El Naqa Issam 
Published: January 2023

AbstractIonizing radiation acoustic imaging (iRAI) allows online monitoring of radiation’s interactions with tissues during radiation therapy, providing real-time, adaptive feedback for cancer treatments. We describe an iRAI volumetric imaging system that enables mapping of the three-dimensional (3D) radiation dose distribution in a complex clinical radiotherapy treatment. The method relies on a two-dimensional matrix array transducer and a matching multi-channel preamplifier board. The feasibility of imaging temporal 3D dose accumulation was first validated in a tissue-mimicking phantom. Next, semiquantitative iRAI relative dose measurements were verified in vivo in a rabbit model. Finally, real-time visualization of the 3D radiation dose delivered to a patient with liver metastases was accomplished with a clinical linear accelerator. These studies demonstrate the potential of iRAI to monitor and quantify the 3D radiation dose deposition during treatment, potentially improving radiotherapy treatment efficacy using real-time adaptive treatment.
In situ cryo-electron tomography reveals the asymmetric architecture of mammalian sperm axonemes
Authors: Chen Zhen , Greenan Garrett A. , Shiozaki Momoko , Liu Yanxin , Skinner Will M. , Zhao Xiaowei , Zhao Shumei , Yan Rui , Yu Zhiheng , Lishko Polina V. , Agard David A. , Vale Ronald D. 
Published: January 2023

AbstractThe flagella of mammalian sperm display non-planar, asymmetric beating, in contrast to the planar, symmetric beating of flagella from sea urchin sperm and unicellular organisms. The molecular basis of this difference is unclear. Here, we perform in situ cryo-electron tomography of mouse and human sperm, providing the highest-resolution structural information to date. Our subtomogram averages reveal mammalian sperm-specific protein complexes within the microtubules, the radial spokes and nexin–dynein regulatory complexes. The locations and structures of these complexes suggest potential roles in enhancing the mechanical strength of mammalian sperm axonemes and regulating dynein-based axonemal bending. Intriguingly, we find that each of the nine outer microtubule doublets is decorated with a distinct combination of sperm-specific complexes. We propose that this asymmetric distribution of proteins differentially regulates the sliding of each microtubule doublet and may underlie the asymmetric beating of mammalian sperm.
Development of Kovacs model for electrical conductivity of carbon nanofiber–polymer systems
Authors: Arjmandi Sajad Khalil , Khademzadeh Yeganeh Jafar , Zare Yasser , Rhee Kyong Yop 
Published: January 2023

AbstractThis study develops a model for electrical conductivity of polymer carbon nanofiber (CNF) nanocomposites (PCNFs), which includes two steps. In the first step, Kovacs model is developed to consider the CNF, interphase and tunneling regions as dissimilar zones in the system. In the second step, simple equations are expressed to estimate the resistances of interphase and tunnels, the volume fraction of CNF and percolation onset. Although some earlier models were proposed to predict the electrical conductivity of PCNFs, developing of Kovacs model causes a better understanding of the effects of main factors on the nanocomposite conductivity. The developed model is supported by logical influences of all factors on the conductivity and by experimented conductivity of several samples. The calculations show good accordance to the experimented data and all factors rationally manage the conductivity of PCNFs. The highest conductivity of PCNF is gained as 0.019 S/m at the lowest ranges of polymer tunnel resistivity (ρ = 500 Ω m) and tunneling distance (d = 2 nm), whereas the highest levels of these factors (ρ > 3000 Ω m and d > 6 nm) cannot cause a conductive sample. Also, high CNF volume fraction, poor waviness, long and thin CNF, low “k”, thick interphase, high CNF conduction, high percentage of percolated CNFs, low percolation onset and high interphase conductivity cause an outstanding conductivity in PCNF.
The clinical significance of radiological changes associated with gliadel implantation in patients with recurrent high grade glioma
Authors: Haim Oz , Agur Ariel , Efrat Or-Tal , Valdes Pablo , Ram Zvi , Grossman Rachel 
Published: January 2023

AbstractGliadel occasionally induces edema following its implantation. We aimed to correlate such post-surgical radiological changes to its efficacy and subsequent survival. Fifty-six patients with recurrent high grade glioma were treated between 2005 and 2016 with Gliadel implantation. Volumetric measurements of MRI features, including FLAIR abnormalities, tumor bulk (volume of gadolinium enhancement on T1) and resection cavity volumes over time were conducted. To assess dynamics over time, linear regression trendlines for each of these were calculated and examined to correlate with survival. Median follow-up after resection was 21.5 months. Median survival post-Gliadel implantation and overall survival since diagnosis were 12 months and 22 months, respectively. A subgroup of patients (n = 6) with a transient increase in FLAIR changes volume over time survived significantly longer post-Gliadel compared to those who did not demonstrate such change (36 vs 12 months, p = .03). Positive trends, representing overall growth in volume over time, of tumor bulk and resection cavity predicted survival in multivariate analyses (hazard ratios 7.9 and 84, p = .003 and .002, respectively). Increase in tumor bulk and resection cavity over time were associated with decreased survival, while transient FLAIR increase was a favorable prognostic factor. This may represent a transient inflammatory process in the tumor, possibly stemming from a presumed immune-mediated anti-tumor response.
Cyst identification in retinal optical coherence tomography images using hidden Markov model
Authors: Mousavi Niloofarsadat , Monemian Maryam , Ghaderi Daneshmand Parisa , Mirmohammadsadeghi Mohammad , Zekri Maryam , Rabbani Hossein 
Published: January 2023

AbstractOptical Coherence Tomography (OCT) is a useful imaging modality facilitating the capturing process from retinal layers. In the salient diseases of retina, cysts are formed in retinal layers. Therefore, the identification of cysts in the retinal layers is of great importance. In this paper, a new method is proposed for the rapid detection of cystic OCT B-scans. In the proposed method, a Hidden Markov Model (HMM) is used for mathematically modelling the existence of cyst. In fact, the existence of cyst in the image can be considered as a hidden state. Since the existence of cyst in an OCT B-scan depends on the existence of cyst in the previous B-scans, HMM is an appropriate tool for modelling this process. In the first phase, a number of features are extracted which are Harris, KAZE, HOG, SURF, FAST, Min-Eigen and feature extracted by deep AlexNet. It is shown that the feature with the best discriminating power is the feature extracted by AlexNet. The features extracted in the first phase are used as observation vectors to estimate the HMM parameters. The evaluation results show the improved performance of HMM in terms of accuracy.
Correlations between linear sprint with the ball, linear sprint without the ball, and change-of-direction without the ball in professional female soccer players
Authors: Preissler Artur Avelino Birk , Schons Pedro , Clemente Filipe Manuel , de Vargas Guilherme Droescher , Klein Lucas Moraes , Silva Ana Filipa , Nobari Hadi , Kruel Luiz Fernando Martins 
Published: January 2023

AbstractThe evolution of female soccer is related to the increase in high-intensity actions and choosing the abilities that best characterize the players' performance. Determining the capabilities that best describe the players' performance becomes essential for coaches and technical staff to obtain the results more efficiently within the competitive calendar. Thus, the study aimed to analyze the correlations between performance in the 20-m sprint tests with and without the ball and the Zigzag 20-m change-of-direction (COD) test without the ball in professional female soccer players. Thirty-three high-level professional female soccer players performed the 20-m sprint tests without a ball, 20-m sprint tests with the ball, and the Zigzag 20-m COD test without the ball. The shortest time obtained in the three trials was used for each test. The fastest time in the three trials was used for each test to calculate the average test speed. The Pearson product–moment correlation test was applied to analyze the correlation between the performance in the tests. Pearson's product–moment correlation test was used to analyze the correlation between the performance in the trials, with a significance level of α < 0.05. The average speed in the 20-m sprint tests with ball showed very large and significant correlations with the speed in the Zigzag 20-m COD test (r = 0.822; p < 0.001; 95% CI = 0.666 to 0.909). The 20-m sprint tests with ball and 20-m sprint tests without ball showed moderate, positive and significant correlation (r = 0.363; p = 0.038; 95% CI = 0.023–0.628). The tests of 20-m sprint tests without ball and Zigzag 20-m COD test also showed moderate, positive and significant correlation (r = 0.415; p = 0.016; 95% CI = 0.084–0.664). The female–female soccer players with a better ability to change direction may also have a better technical ability to drive the ball at high speed. However, they will not necessarily be the fastest in the linear sprint without the ball. Coaches and technical staff may choose to perform tests seeking efficiency and practicality, especially in a congested competitive period.