bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibiting BCKDK in triple negative breast cancer suppresses protein translation, impairs mitochondrial function, and potentiates doxorubicin cytotoxicity
Authors: Biswas Dipsikha , Slade Logan , Duffley Luke , Mueller Neil , Dao Khoi Thien , Mercer Angella , Pakkiriswami Shanmugasundaram , El Hiani Yassine , Kienesberger Petra C. , Pulinilkunnil Thomas 
Published: September 2021

AbstractTriple-negative breast cancers (TNBCs) are characterized by poor survival, prognosis, and gradual resistance to cytotoxic chemotherapeutics, like doxorubicin (DOX). The clinical utility of DOX is limited by its cardiotoxic and chemoresistant effects that manifest over time. To induce chemoresistance, TNBC rewires oncogenic gene expression and cell signaling pathways. Recent studies have demonstrated that reprogramming of branched-chain amino acids (BCAAs) metabolism facilitates tumor growth and survival. Branched-chain ketoacid dehydrogenase kinase (BCKDK), a regulatory kinase of the rate-limiting enzyme of the BCAA catabolic pathway, is reported to activate RAS/RAF/MEK/ERK signaling to promote tumor cell proliferation. However, it remains unexplored if BCKDK action remodels TNBC proliferation and survival per se and influences susceptibility to DOX-induced genotoxic stress. TNBC cells treated with DOX exhibited reduced BCKDK expression and intracellular BCKAs. Genetic and pharmacological inhibition of BCKDK in TNBC cell lines also showed a similar reduction in intracellular and secreted BCKAs. BCKDK silencing in TNBC cells downregulated mitochondrial metabolism genes, reduced electron complex protein expression, oxygen consumption, and ATP production. Transcriptome analysis of BCKDK silenced cells confirmed dysregulation of mitochondrial metabolic networks and upregulation of the apoptotic signaling pathway. Furthermore, BCKDK inhibition with concurrent DOX treatment exacerbated apoptosis, caspase activity, and loss of TNBC proliferation. Inhibition of BCKDK in TNBC also upregulated sestrin 2 and concurrently decreased mTORC1 signaling and protein synthesis. Overall, loss of BCKDK action in TNBC remodels BCAA flux, reduces protein translation triggering cell death, ATP insufficiency, and susceptibility to genotoxic stress.
Blue food demand across geographic and temporal scales
Authors: Naylor Rosamond L. , Kishore Avinash , Sumaila U. Rashid , Issifu Ibrahim , Hunter Blaire P. , Belton Ben , Bush Simon R. , Cao Ling , Gelcich Stefan , Gephart Jessica A. , Golden Christopher D. , Jonell Malin , Koehn J. Zachary , Little David C. , Thilsted Shakuntala H. , Tigchelaar Michelle , Crona Beatrice 
Published: September 2021

AbstractNumerous studies have focused on the need to expand production of ‘blue foods’, defined as aquatic foods captured or cultivated in marine and freshwater systems, to meet rising population- and income-driven demand. Here we analyze the roles of economic, demographic, and geographic factors and preferences in shaping blue food demand, using secondary data from FAO and The World Bank, parameters from published models, and case studies at national to sub-national scales. Our results show a weak cross-sectional relationship between per capita income and consumption globally when using an aggregate fish metric. Disaggregation by fish species group reveals distinct geographic patterns; for example, high consumption of freshwater fish in China and pelagic fish in Ghana and Peru where these fish are widely available, affordable, and traditionally eaten. We project a near doubling of global fish demand by mid-century assuming continued growth in aquaculture production and constant real prices for fish. Our study concludes that nutritional and environmental consequences of rising demand will depend on substitution among fish groups and other animal source foods in national diets.
Δ133p53β isoform pro-invasive activity is regulated through an aggregation-dependent mechanism in cancer cells
Authors: Arsic Nikola , Slatter Tania , Gadea Gilles , Villain Etienne , Fournet Aurelie , Kazantseva Marina , Allemand Frédéric , Sibille Nathalie , Seveno Martial , de Rossi Sylvain , Mehta Sunali , Urbach Serge , Bourdon Jean-Christophe , Bernado Pau , Kajava Andrey V. , Braithwaite Antony , Roux Pierre 
Published: September 2021

AbstractThe p53 isoform, Δ133p53β, is critical in promoting cancer. Here we report that Δ133p53β activity is regulated through an aggregation-dependent mechanism. Δ133p53β aggregates were observed in cancer cells and tumour biopsies. The Δ133p53β aggregation depends on association with interacting partners including p63 family members or the CCT chaperone complex. Depletion of the CCT complex promotes accumulation of Δ133p53β aggregates and loss of Δ133p53β dependent cancer cell invasion. In contrast, association with p63 family members recruits Δ133p53β from aggregates increasing its intracellular mobility. Our study reveals novel mechanisms of cancer progression for p53 isoforms which are regulated through sequestration in aggregates and recruitment upon association with specific partners like p63 isoforms or CCT chaperone complex, that critically influence cancer cell features like EMT, migration and invasion.
C3 complement inhibition prevents antibody-mediated rejection and prolongs renal allograft survival in sensitized non-human primates
Authors: Schmitz Robin , Fitch Zachary W. , Schroder Paul M. , Choi Ashley Y. , Manook Miriam , Yoon Janghoon , Song Mingqing , Yi John S. , Khandelwal Sanjay , Arepally Gowthami M. , Farris Alton B. , Reis Edimara S. , Lambris John D. , Kwun Jean , Knechtle Stuart J. 
Published: September 2021

AbstractSensitized kidney transplant recipients experience high rates of antibody-mediated rejection due to the presence of donor-specific antibodies and immunologic memory. Here we show that transient peri-transplant treatment with the central complement component C3 inhibitor Cp40 significantly prolongs median allograft survival in a sensitized nonhuman primate model. Despite donor-specific antibody levels remaining high, fifty percent of Cp40-treated primates maintain normal kidney function beyond the last day of treatment. Interestingly, presence of antibodies of the IgM class associates with reduced median graft survival (8 vs. 40 days;p = 0.02). Cp40 does not alter lymphocyte depletion by rhesus-specific anti-thymocyte globulin, but inhibits lymphocyte activation and proliferation, resulting in reduced antibody-mediated injury and complement deposition. In summary, Cp40 prevents acute antibody-mediated rejection and prolongs graft survival in primates, and inhibits T and B cell activation and proliferation, suggesting an immunomodulatory effect beyond its direct impact on antibody-mediated injury.
A prostate-specific membrane antigen activated molecular rotor for real-time fluorescence imaging
Authors: Zhang Jingming , Rakhimbekova Anastasia , Duan Xiaojiang , Yin Qingqing , Foss Catherine A. , Fan Yan , Xu Yangyang , Li Xuesong , Cai Xuekang , Kutil Zsofia , Wang Pengyuan , Yang Zhi , Zhang Ning , Pomper Martin G. , Wang Yiguang , Bařinka Cyril , Yang Xing 
Published: September 2021

AbstractSurgery is an efficient way to treat localized prostate cancer (PCa), however, it is challenging to demarcate rapidly and accurately the tumor boundary intraoperatively, as existing tumor detection methods are seldom performed in real-time. To overcome those limitations, we develop a fluorescent molecular rotor that specifically targets the prostate-specific membrane antigen (PSMA), an established marker for PCa. The probes have picomolar affinity (IC50 = 63-118 pM) for PSMA and generate virtually instantaneous onset of robust fluorescent signal proportional to the concentration of the PSMA-probe complex. In vitro and ex vivo experiments using PCa cell lines and clinical samples, respectively, indicate the utility of the probe for biomedical applications, including real-time monitoring of endocytosis and tumor staging. Experiments performed in a PCa xenograft model reveal suitability of the probe for imaging applications in vivo.
Spin/valley pumping of resident electrons in WSe2 and WS2 monolayers
Authors: Robert Cedric , Park Sangjun , Cadiz Fabian , Lombez Laurent , Ren Lei , Tornatzky Hans , Rowe Alistair , Paget Daniel , Sirotti Fausto , Yang Min , Van Tuan Dinh , Taniguchi Takashi , Urbaszek Bernhard , Watanabe Kenji , Amand Thierry , Dery Hanan , Marie Xavier 
Published: September 2021

AbstractMonolayers of transition metal dichalcogenides are ideal materials to control both spin and valley degrees of freedom either electrically or optically. Nevertheless, optical excitation mostly generates excitons species with inherently short lifetime and spin/valley relaxation time. Here we demonstrate a very efficient spin/valley optical pumping of resident electrons in n-doped WSe2 and WS2 monolayers. We observe that, using a continuous wave laser and appropriate doping and excitation densities, negative trion doublet lines exhibit circular polarization of opposite sign and the photoluminescence intensity of the triplet trion is more than four times larger with circular excitation than with linear excitation. We interpret our results as a consequence of a large dynamic polarization of resident electrons using circular light.
Chlamydia evasion of neutrophil host defense results in NLRP3 dependent myeloid-mediated sterile inflammation through the purinergic P2X7 receptor
Authors: Yang Chunfu , Lei Lei , Collins John W. Marshall , Briones Michael , Ma Li , Sturdevant Gail L. , Su Hua , Kashyap Anuj K. , Dorward David , Bock Kevin W. , Moore Ian N. , Bonner Christine , Chen Chih-Yu , Martens Craig A. , Ricklefs Stacy , Yamamoto Masahiro , Takeda Kiyoshi , Iwakura Yoichiro , McClarty Grant , Caldwell Harlan D. 
Published: September 2021

AbstractChlamydia trachomatis infection causes severe inflammatory disease resulting in blindness and infertility. The pathophysiology of these diseases remains elusive but myeloid cell-associated inflammation has been implicated. Here we show NLRP3 inflammasome activation is essential for driving a macrophage-associated endometritis resulting in infertility by using a female mouse genital tract chlamydial infection model. We find the chlamydial parasitophorous vacuole protein CT135 triggers NLRP3 inflammasome activation via TLR2/MyD88 signaling as a pathogenic strategy to evade neutrophil host defense. Paradoxically, a consequence of CT135 mediated neutrophil killing results in a submucosal macrophage-associated endometritis driven by ATP/P2X7R induced NLRP3 inflammasome activation. Importantly, macrophage-associated immunopathology occurs independent of macrophage infection. We show chlamydial infection of neutrophils and epithelial cells produce elevated levels of extracellular ATP. We propose this source of ATP serves as a DAMP to activate submucosal macrophage NLRP3 inflammasome that drive damaging immunopathology. These findings offer a paradigm of sterile inflammation in infectious disease pathogenesis.
Magnetoelectric phase transition driven by interfacial-engineered Dzyaloshinskii-Moriya interaction
Authors: Liu Xin , Song Wenjie , Wu Mei , Yang Yuben , Yang Ying , Lu Peipei , Tian Yinhua , Sun Yuanwei , Lu Jingdi , Wang Jing , Yan Dayu , Shi Youguo , Sun Nian Xiang , Sun Young , Gao Peng , Shen Ka , Chai Guozhi , Kou Supeng , Nan Ce-Wen , Zhang Jinxing 
Published: September 2021

AbstractStrongly correlated oxides with a broken symmetry could exhibit various phase transitions, such as superconductivity, magnetism and ferroelectricity. Construction of superlattices using these materials is effective to design crystal symmetries at atomic scale for emergent orderings and phases. Here, antiferromagnetic Ruddlesden-Popper Sr2IrO4 and perovskite paraelectric (ferroelectric) SrTiO3 (BaTiO3) are selected to epitaxially fabricate superlattices for symmetry engineering. An emergent magnetoelectric phase transition is achieved in Sr2IrO4/SrTiO3 superlattices with artificially designed ferroelectricity, where an observable interfacial Dzyaloshinskii-Moriya interaction driven by non-equivalent interface is considered as the microscopic origin. By further increasing the polarization namely interfacial Dzyaloshinskii-Moriya interaction via replacing SrTiO3 with BaTiO3, the transition temperature can be enhanced from 46 K to 203 K, accompanying a pronounced magnetoelectric coefficient of ~495 mV/cm·Oe. This interfacial engineering of Dzyaloshinskii-Moriya interaction provides a strategy to design quantum phases and orderings in correlated electron systems.
A deep-learning framework for multi-level peptide–protein interaction prediction
Authors: Lei Yipin , Li Shuya , Liu Ziyi , Wan Fangping , Tian Tingzhong , Li Shao , Zhao Dan , Zeng Jianyang 
Published: September 2021

AbstractPeptide-protein interactions are involved in various fundamental cellular functions and their identification is crucial for designing efficacious peptide therapeutics. Recently, a number of computational methods have been developed to predict peptide-protein interactions. However, most of the existing prediction approaches heavily depend on high-resolution structure data. Here, we present a deep learning framework for multi-level peptide-protein interaction prediction, called CAMP, including binary peptide-protein interaction prediction and corresponding peptide binding residue identification. Comprehensive evaluation demonstrated that CAMP can successfully capture the binary interactions between peptides and proteins and identify the binding residues along the peptides involved in the interactions. In addition, CAMP outperformed other state-of-the-art methods on binary peptide-protein interaction prediction. CAMP can serve as a useful tool in peptide-protein interaction prediction and identification of important binding residues in the peptides, which can thus facilitate the peptide drug discovery process.
Analysis of 427 genomes reveals moso bamboo population structure and genetic basis of property traits
Authors: Zhao Hansheng , Sun Shuai , Ding Yulong , Wang Yue , Yue Xianghua , Du Xiao , Wei Qiang , Fan Guangyi , Sun Huayu , Lou Yongfeng , Yang Huanming , Wang Jian , Xu Xun , Li Lichao , Yang Kebin , Xu Hao , Wang Jiongliang , Zhu Chenglei , Wang Sining , Shan Xuemeng , Hou Yinguang , Wang Yu , Fei Benhua , Liu Xin , Jiang Zehui , Gao Zhimin 
Published: September 2021

AbstractMoso bamboo (Phyllostachys edulis) is an economically and ecologically important nontimber forestry species. Further development of this species as a sustainable bamboo resource has been hindered by a lack of population genome information. Here, we report a moso bamboo genomic variation atlas of 5.45 million single-nucleotide polymorphisms (SNPs) from whole-genome resequencing of 427 individuals covering 15 representative geographic areas. We uncover low genetic diversity, high genotype heterozygosity, and genes under balancing selection underlying moso bamboo population adaptation. We infer its demographic history with one bottleneck and its recently small population without a rebound. We define five phylogenetic groups and infer that one group probably originated by a single-origin event from East China. Finally, we conduct genome-wide association analysis of nine important property-related traits to identify candidate genes, many of which are involved in cell wall, carbohydrate metabolism, and environmental adaptation. These results provide a foundation and resources for understanding moso bamboo evolution and the genetic mechanisms of agriculturally important traits.
Strong and ductile Fe-24Mn-3Cr alloy resistant against erosion-corrosion
Authors: Jeong Yeong Jae , Kim Si On , Park Jin Sung , Lee Jae Won , Hwang Joong-Ki , Lee Soon Gi , Choi Jong Kyo , Kim Sung Jin 
Published: September 2021

AbstractThe ternary-based Fe-24Mn-3Cr alloy has superior mechanical properties based on an attractive combination of high strength and ductility, with long-term environmental stability in highly corrosive environments compared to conventional ferritic steel alloys. This study reports that the environmental instability caused by the rapid electrochemical corrosion kinetics on the surface of conventional high Mn-bearing ferrous alloys could be overcome by a combination of high Mn–low Cr-balanced Fe and their synergistic interactions. In contrast to Cr-free Mn-bearing alloys, the high Mn–low Cr-bearing alloy showed comparatively lower corrosion kinetic parameters, without a continuously increasing trend, and higher polarization resistance according to electrochemical polarization and impedance spectroscopy measurements. Moreover, the rate of degradation caused by erosion–corrosion synergistic interaction under erosion–corrosion dynamic flow conditions was the lowest in the high Mn–low Cr-bearing alloy. These surface-inhibiting characteristics of the alloy were attributed primarily to the formation of a bilayer scale structure consisting of inner α-Fe2−xCrxO3/outer FexMn3−xO4on the surface.
Usefulness analysis of the 2018 ASCO/IDSA guideline for outpatient management of fever and neutropenia in adults treated for malignancy
Authors: Hwang Soyoon , Kwon Ki Tae , Kim Yoonjung , Bae Sohyun , Chang Hyun-Ha , Kim Shin-Woo , Yoo Seung Soo , Nam Su Youn , Baek Jin Ho 
Published: September 2021

AbstractAlthough the clinical practice guideline for outpatient management of febrile neutropenia (FN) in adults treated for malignancy was updated by the ASCO/IDSA in 2018, most patients with FN in our hospital have been hospitalized. We performed this study to analyze the usefulness of the guideline. The medical records of patients hospitalized for FN in Kyungpook National University Chilgok Hospital from May 2016 to April 2018 were retrospectively reviewed. The feasibility of candidates for outpatient management according to the guideline was evaluated based on the outcomes. A total of 114 patients were enrolled and categorized into two groups, low-risk (38.6%) and high-risk (61.4%). The proportion of feasible candidates for outpatient management was 70.2% and was higher in the low-risk than in the high-risk group (90.0% vs. 57.1%; P < 0.001). The low-risk group had no mortality, no resistance to oral amoxicillin/clavulanate or ciprofloxacin, a higher rate of successful empirical antibiotics, and lower rates of glycopeptide or carbapenem administration. A significant number of hospitalized cancer patients treated for FN after chemotherapy were found to be feasible candidates for outpatient management. The guideline can be a useful tool to reduce labor of healthcare workers and hospitalization costs.
Patient characteristics, treatment patterns, and outcomes of Rickettsial diseases among a commercially insured population in the United States, 2005–2017
Authors: Binder Alison M. , Armstrong Paige A. 
Published: September 2021

AbstractRickettsial diseases (RDs) are transmitted to humans by ectoparasites, including ticks and fleas. Symptoms range from mild febrile illness, to severe disease or death. Doxycycline is the treatment of choice for patients of all ages; early treatment based on clinical diagnosis is critical to prevent severe outcomes. We conducted a descriptive analysis using insurance claims data captured by IBM MarketScan® research databases to describe demographics, treatment patterns, and outcomes of patients diagnosed with RDs in the United States during 2005–2017. Overall, 14,830 patients had a RD diagnosis during 2005–2017; 7,517 (50.7%) spotted fever rickettsiosis (SFR), 4,571 ( 30.8%) ehrlichiosis, 1,362 (9.2%) typhus group rickettsiosis (TGR), and 1,193 (8.0%) other rickettsial diseases. Among all patients diagnosed, 53.1% received doxycycline. Prescription rates varied by diagnosis and age; 24.1% of TGR and 61.1% of SFR patients received doxycycline; 23.9% of persons < 8 years received doxycycline, compared with 47.7% for 8–17 years, and 55.4% for ≥ 18 years. RDs are frequently diagnosed in the outpatient population; however, providers prescribed the recommended treatment to about half of patients. Continued education of treatment recommendations is critical to prevent severe outcomes.
Towards reliable diagnostics of prostate cancer via breath
Authors: Maiti K. S. , Fill E. , Strittmatter F. , Volz Y. , Sroka R. , Apolonski A. 
Published: September 2021

AbstractEarly detection of cancer is a key ingredient for saving many lives. Unfortunately, cancers of the urogenital system are difficult to detect at early stage. The existing noninvasive diagnostics of prostate cancer (PCa) suffer from low accuracy (< 70%) even at advanced stages. In an attempt to improve the accuracy, a small breath study of 63 volunteers representing three groups: (1) of 19 healthy, (2) 28 with PCa, (3) with 8 kidney cancer (KC) and 8 bladder cancer (BC) was performed. Ultrabroadband mid-infrared Fourier absorption spectroscopy revealed eight spectral ranges (SRs) that differentiate the groups. The resulting accuracies of supervised analyses exceeded 95% for four SRs in distinguishing (1) vs (2), three for (1) vs (3) and four SRs for (1) vs (2) + (3). The SRs were then attributed to volatile metabolites. Their origin and involvement in urogenital carcinogenesis are discussed.
Functionally diverse heteromeric traps for ligands of the transforming growth factor-β superfamily
Authors: Kumar Ravindra , Grinberg Asya V. , Li Huiming , Kuo Tzu-Hsing , Sako Dianne , Krishnan Lavanya , Liharska Katia , Li Jia , Grenha Rosa , Maguire Michelle C. , Briscoe Steven D. , Pearsall R. Scott , Herrin Brantley R. , Suragani Rajasekhar N. V. S. , Castonguay Roselyne 
Published: September 2021

AbstractLigands of the transforming growth factor-β (TGF-β) superfamily are important targets for therapeutic intervention but present challenges because they signal combinatorially and exhibit overlapping activities in vivo. To obtain agents capable of sequestering multiple TGF-β superfamily ligands with novel selectivity, we generated soluble, heterodimeric ligand traps by pairing the extracellular domain (ECD) of the native activin receptor type IIB (ActRIIB) alternately with the ECDs of native type I receptors activin receptor-like kinase 4 (ALK4), ALK7, or ALK3. Systematic analysis of these heterodimeric constructs by surface plasmon resonance, and comparison with their homodimeric counterparts, revealed that each type I receptor partner confers a distinct ligand-binding profile to the heterodimeric construct. Additional characterization in cell-based reporter gene assays confirmed that the heterodimeric constructs possessed different profiles of signaling inhibition in vitro, which translated into altered patterns of pharmacological activity when constructs were administered systemically to wild-type mice. Our results detail a versatile platform for the modular recombination of naturally occurring receptor domains, giving rise to inhibitory ligand traps that could aid in defining the physiological roles of TGF-β ligand sets or be directed therapeutically to human diseases arising from dysregulated TGF-β superfamily signaling.