bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of the first cultured free-living representative of Candidatus Izemoplasma uncovers its unique biology
Authors: Zheng Rikuan , Liu Rui , Shan Yeqi , Cai Ruining , Liu Ge , Sun Chaomin 
Published: March 2021

Abstract
Candidatus Izemoplasma, an intermediate in the reductive evolution from Firmicutes to Mollicutes, was proposed to represent a novel class of free-living wall-less bacteria within the phylum Tenericutes. Unfortunately, the paucity of pure cultures has limited further insights into their physiological and metabolic features as well as ecological roles. Here, we report the first successful isolation of an Izemoplasma representative from the deep-sea methane seep, strain zrk13, using a DNA degradation-driven method given Izemoplasma’s prominent DNA-degradation potentials. We further present a detailed description of the physiological, genomic and metabolic traits of the novel strain, which allows for the first time the reconstruction of the metabolic potential and lifestyle of a member of the tentatively defined Candidatus Izemoplasma. On the basis of the description of strain zrk13, the novel species and genus Xianfuyuplasma coldseepsis is proposed. Using a combined biochemical and transcriptomic method, we further show the supplement of organic matter, thiosulfate or bacterial genomic DNA could evidently promote the growth of strain zrk13. In particular, strain zrk13 could degrade and utilize the extracellular DNA for growth in both laboraterial and deep-sea conditions. Moreover, the predicted genes determining DNA-degradation broadly distribute in the genomes of other Izemoplasma members. Given that extracellular DNA is a particularly crucial phosphorus as well as nitrogen and carbon source for microorganisms in the seafloor, Izemoplasma bacteria are thought to be important contributors to the biogeochemical cycling in the deep ocean.
Functional tissue-engineered bone-like graft made of a fibrin scaffold and TG2 gene-modified EMSCs for bone defect repair
Authors: Shi Wentao , Que Yunduan , Zhang Xuan , Bian Lu , Yu Xuejian , Tang Xue , Yang Guofeng , Dai Yao , Bi Shiqi , Lv Demin , Weng Yuyan , Wu Weijiang , Zhang Zhijian , Lu Xiaojie , Lu Naiyan 
Published: March 2021

AbstractThe transplantation of tissue-engineered scaffolds with stem cells is a promising therapeutic approach for bone defect repair. To improve the therapeutic efficacy of this approach, in this study, a novel biofunctional live tissue-engineered bone-like graft was designed and constructed using a fibrin scaffold loaded with TG2 gene-modified ectomesenchymal stem cells (TG2-EMSCs) derived from nasal respiratory mucosa for bone defect repair. Autocalcification of the cell-free fibrin gel in osteogenic medium with additional alkaline phosphatase (ALP) and the osteogenic differentiation of TG2-EMSCs on the fibrin scaffold were assessed in vitro. The results indicated that the cell-free fibrin gel could autocalcify in the osteogenic medium with ALP and that the overexpression of TG2 by TG2-EMSCs could promote the osteogenic differentiation of these stem cells in the fibrin scaffold. Moreover, TG2 could enhance the deposition of extracellular matrix proteins in the fibrin scaffold, followed by calcification of the bone matrix in vitro. After transplantation into critical-sized cranial defects in rats, the functional tissue-engineered bone-like grafts improved bone regeneration. These results indicate that this tissue-engineered bone-like graft could improve the process of bone defect repair.
Ocular coloboma—a comprehensive review for the clinician
Authors: Lingam Gopal , Sen Alok C. , Lingam Vijaya , Bhende Muna , Padhi Tapas Ranjan , Xinyi Su 
Published: March 2021

AbstractTypical ocular coloboma is caused by defective closure of the embryonal fissure. The occurrence of coloboma can be sporadic, hereditary (known or unknown gene defects) or associated with chromosomal abnormalities. Ocular colobomata are more often associated with systemic abnormalities when caused by chromosomal abnormalities. The ocular manifestations vary widely. At one extreme, the eye is hardly recognisable and non-functional—having been compressed by an orbital cyst, while at the other, one finds minimalistic involvement that hardly affects the structure and function of the eye. In the fundus, the variability involves the size of the coloboma (anteroposterior and transverse extent) and the involvement of the optic disc and fovea. The visual acuity is affected when coloboma involves disc and fovea, or is complicated by occurrence of retinal detachment, choroidal neovascular membrane, cataract, amblyopia due to uncorrected refractive errors, etc. While the basic birth anomaly cannot be corrected, most of the complications listed above are correctable to a great extent. Current day surgical management of coloboma-related retinal detachments has evolved to yield consistently good results. Cataract surgery in these eyes can pose a challenge due to a combination of microphthalmos and relatively hard lenses, resulting in increased risk of intra-operative complications. Prophylactic laser retinopexy to the border of choroidal coloboma appears to be an attractive option for reducing risk of coloboma-related retinal detachment. However, a majority of the eyes have the optic disc within the choroidal coloboma, thus making it difficult to safely administer a complete treatment.
Bora phosphorylation substitutes in trans for T-loop phosphorylation in Aurora A to promote mitotic entry
Authors: Tavernier N. , Thomas Y. , Vigneron S. , Maisonneuve P. , Orlicky S. , Mader P. , Regmi S. G. , Van Hove L. , Levinson N. M. , Gasmi-Seabrook G. , Joly N. , Poteau M. , Velez-Aguilera G. , Gavet O. , Castro A. , Dasso M. , Lorca T. , Sicheri F. , Pintard L. 
Published: March 2021

AbstractPolo-like kinase 1 (Plk1) is instrumental for mitotic entry and progression. Plk1 is activated by phosphorylation on a conserved residue Thr210 in its activation segment by the Aurora A kinase (AURKA), a reaction that critically requires the co-factor Bora phosphorylated by a CyclinA/B-Cdk1 kinase. Here we show that phospho-Bora is a direct activator of AURKA kinase activity. We localize the key determinants of phospho-Bora function to a 100 amino acid region encompassing two short Tpx2-like motifs and a phosphoSerine-Proline motif at Serine 112, through which Bora binds AURKA. The latter substitutes in trans for the Thr288 phospho-regulatory site of AURKA, which is essential for an active conformation of the kinase domain. We demonstrate the importance of these determinants for Bora function in mitotic entry both in Xenopus egg extracts and in human cells. Our findings unveil the activation mechanism of AURKA that is critical for mitotic entry.
The oncogene AAMDC links PI3K-AKT-mTOR signaling with metabolic reprograming in estrogen receptor-positive breast cancer
Authors: Golden Emily , Rashwan Rabab , Woodward Eleanor A. , Sgro Agustin , Wang Edina , Sorolla Anabel , Waryah Charlene , Tie Wan Jun , Cuyàs Elisabet , Ratajska Magdalena , Kardaś Iwona , Kozlowski Piotr , Johnstone Elizabeth K. M. , See Heng B. , Duffy Ciara , Parry Jeremy , Lagerborg Kim A. , Czapiewski Piotr , Menendez Javier A. , Gorczyński Adam , Wasag Bartosz , Pfleger Kevin D. G. , Curtis Christina , Lee Bum-Kyu , Kim Jonghwan , Cursons Joseph , Pavlos Nathan J. , Biernat Wojciech , Jain Mohit , Woo Andrew J. , Redfern Andrew , Blancafort Pilar 
Published: March 2021

AbstractAdipogenesis associated Mth938 domain containing (AAMDC) represents an uncharacterized oncogene amplified in aggressive estrogen receptor-positive breast cancers. We uncover that AAMDC regulates the expression of several metabolic enzymes involved in the one-carbon folate and methionine cycles, and lipid metabolism. We show that AAMDC controls PI3K-AKT-mTOR signaling, regulating the translation of ATF4 and MYC and modulating the transcriptional activity of AAMDC-dependent promoters. High AAMDC expression is associated with sensitization to dactolisib and everolimus, and these PI3K-mTOR inhibitors exhibit synergistic interactions with anti-estrogens in IntClust2 models. Ectopic AAMDC expression is sufficient to activate AKT signaling, resulting in estrogen-independent tumor growth. Thus, AAMDC-overexpressing tumors may be sensitive to PI3K-mTORC1 blockers in combination with anti-estrogens. Lastly, we provide evidence that AAMDC can interact with the RabGTPase-activating protein RabGAP1L, and that AAMDC, RabGAP1L, and Rab7a colocalize in endolysosomes. The discovery of the RabGAP1L-AAMDC assembly platform provides insights for the design of selective blockers to target malignancies having the AAMDC amplification.
Multi-pronged neuromodulation intervention engages the residual motor circuitry to facilitate walking in a rat model of spinal cord injury
Authors: Bonizzato Marco , James Nicholas D. , Pidpruzhnykova Galyna , Pavlova Natalia , Shkorbatova Polina , Baud Laetitia , Martinez-Gonzalez Cristina , Squair Jordan W. , DiGiovanna Jack , Barraud Quentin , Micera Silvestro , Courtine Gregoire 
Published: March 2021

AbstractA spinal cord injury usually spares some components of the locomotor circuitry. Deep brain stimulation (DBS) of the midbrain locomotor region and epidural electrical stimulation of the lumbar spinal cord (EES) are being used to tap into this spared circuitry to enable locomotion in humans with spinal cord injury. While appealing, the potential synergy between DBS and EES remains unknown. Here, we report the synergistic facilitation of locomotion when DBS is combined with EES in a rat model of severe contusion spinal cord injury leading to leg paralysis. However, this synergy requires high amplitudes of DBS, which triggers forced locomotion associated with stress responses. To suppress these undesired responses, we link DBS to the intention to walk, decoded from cortical activity using a robust, rapidly calibrated unsupervised learning algorithm. This contingency amplifies the supraspinal descending command while empowering the rats into volitional walking. However, the resulting improvements may not outweigh the complex technological framework necessary to establish viable therapeutic conditions.
Single-cell analyses of Crohn’s disease tissues reveal intestinal intraepithelial T cells heterogeneity and altered subset distributions
Authors: Jaeger Natalia , Gamini Ramya , Cella Marina , Schettini Jorge L. , Bugatti Mattia , Zhao Shanrong , Rosadini Charles V. , Esaulova Ekaterina , Di Luccia Blanda , Kinnett Baylee , Vermi William , Artyomov Maxim N. , Wynn Thomas A. , Xavier Ramnik J. , Jelinsky Scott A. , Colonna Marco 
Published: March 2021

AbstractCrohn’s disease (CD) is a chronic transmural inflammation of intestinal segments caused by dysregulated interaction between microbiome and gut immune system. Here, we profile, via multiple single-cell technologies, T cells purified from the intestinal epithelium and lamina propria (LP) from terminal ileum resections of adult severe CD cases. We find that intraepithelial lymphocytes (IEL) contain several unique T cell subsets, including NKp30+γδT cells expressing RORγt and producing IL-26 upon NKp30 engagement. Further analyses comparing tissues from non-inflamed and inflamed regions of patients with CD versus healthy controls show increased activated TH17 but decreased CD8+T, γδT, TFH and Treg cells in inflamed tissues. Similar analyses of LP find increased CD8+, as well as reduced CD4+T cells with an elevated TH17 over Treg/TFH ratio. Our analyses of CD tissues thus suggest a potential link, pending additional validations, between transmural inflammation, reduced IEL γδT cells and altered spatial distribution of IEL and LP T cell subsets.
Cardiac macrophages prevent sudden death during heart stress
Authors: Sugita Junichi , Fujiu Katsuhito , Nakayama Yukiteru , Matsubara Takumi , Matsuda Jun , Oshima Tsukasa , Liu Yuxiang , Maru Yujin , Hasumi Eriko , Kojima Toshiya , Seno Hiroshi , Asano Keisuke , Ishijima Ayumu , Tomii Naoki , Yamazaki Masatoshi , Kudo Fujimi , Sakuma Ichiro , Nagai Ryozo , Manabe Ichiro , Komuro Issei 
Published: March 2021

AbstractCardiac arrhythmias are a primary contributor to sudden cardiac death, a major unmet medical need. Because right ventricular (RV) dysfunction increases the risk for sudden cardiac death, we examined responses to RV stress in mice. Among immune cells accumulated in the RV after pressure overload-induced by pulmonary artery banding, interfering with macrophages caused sudden death from severe arrhythmias. We show that cardiac macrophages crucially maintain cardiac impulse conduction by facilitating myocardial intercellular communication through gap junctions. Amphiregulin (AREG) produced by cardiac macrophages is a key mediator that controls connexin 43 phosphorylation and translocation in cardiomyocytes. Deletion of Areg from macrophages led to disorganization of gap junctions and, in turn, lethal arrhythmias during acute stresses, including RV pressure overload and β-adrenergic receptor stimulation. These results suggest that AREG from cardiac resident macrophages is a critical regulator of cardiac impulse conduction and may be a useful therapeutic target for the prevention of sudden death.
Non-equilibrium properties of an active nanoparticle in a harmonic potential
Authors: Schmidt Falko , Šípová-Jungová Hana , Käll Mikael , Würger Alois , Volpe Giovanni 
Published: March 2021

AbstractActive particles break out of thermodynamic equilibrium thanks to their directed motion, which leads to complex and interesting behaviors in the presence of confining potentials. When dealing with active nanoparticles, however, the overwhelming presence of rotational diffusion hinders directed motion, leading to an increase of their effective temperature, but otherwise masking the effects of self-propulsion. Here, we demonstrate an experimental system where an active nanoparticle immersed in a critical solution and held in an optical harmonic potential features far-from-equilibrium behavior beyond an increase of its effective temperature. When increasing the laser power, we observe a cross-over from a Boltzmann distribution to a non-equilibrium state, where the particle performs fast orbital rotations about the beam axis. These findings are rationalized by solving the Fokker-Planck equation for the particle’s position and orientation in terms of a moment expansion. The proposed self-propulsion mechanism results from the particle’s non-sphericity and the lower critical point of the solution.
Co-dependency for MET and FGFR1 in basal triple-negative breast cancers
Authors: Sung Vanessa Y. C. , Knight Jennifer F. , Johnson Radia M. , Stern Yaakov E. , Saleh Sadiq M. , Savage Paul , Monast Anie , Zuo Dongmei , Duhamel Stéphanie , Park Morag 
Published: March 2021

AbstractTriple-negative breast cancer (TNBC) is a heterogeneous disease that lacks both effective patient stratification strategies and therapeutic targets. Whilst elevated levels of the MET receptor tyrosine kinase are associated with TNBCs and predict poor clinical outcome, the functional role of MET in TNBC is still poorly understood. In this study, we utilise an established Met-dependent transgenic mouse model of TNBC, human cell lines and patient-derived xenografts to investigate the role of MET in TNBC tumorigenesis. We find that in TNBCs with mesenchymal signatures, MET participates in a compensatory interplay with FGFR1 to regulate tumour-initiating cells (TICs). We demonstrate a requirement for the scaffold protein FRS2 downstream from both Met and FGFR1 and find that dual inhibition of MET and FGFR1 signalling results in TIC depletion, hindering tumour progression. Importantly, basal breast cancers that display elevated MET and FGFR1 signatures are associated with poor relapse-free survival. Our results support a role for MET and FGFR1 as potential co-targets for anti-TIC therapies in TNBC.
The HSP70-fused foot-and-mouth disease epitope elicits cellular and humoral immunity and drives broad-spectrum protective efficacy
Authors: Jo Hyundong , Kim Bong Yoon , Park So Hui , Kim Hyun Mi , Shin Sung Ho , Hwang Seong Yun , Kim Su-Mi , Kim Byounghan , Park Jong-Hyeon , Lee Min Ja 
Published: March 2021

AbstractCurrent foot-and-mouth disease (FMD) vaccines have significant limitations, including side effects due to oil emulsions at the vaccination site, a narrow spectrum of protective efficacy, and incomplete host defenses mediated by humoral immunity alone. To overcome these limitations, new FMD vaccines must ensure improved safety with non-oil-based adjuvants, a broad spectrum of host defenses within/between serotypes, and the simultaneous induction of cellular and humoral immunity. We designed a novel, immune-potent, recombinant protein rpHSP70-AD that induces robust cellular immunity and elicits a broad spectrum of host defenses against FMD virus (FMDV) infections. We demonstrated that an oil emulsion-free vaccine containing rpHSP70-AD mediates early, mid-term, and long-term immunity and drives potent host protection against FMDV type O and A, suggesting its potential as an FMD vaccine adjuvant in mice and pigs. These results suggest a key strategy for establishing next-generation FMD vaccines, including novel adjuvants.
Downscaling GRACE total water storage change using partial least squares regression
Authors: Vishwakarma Bramha Dutt , Zhang Jinwei , Sneeuw Nico 
Published: March 2021

AbstractThe Gravity Recovery And Climate Experiment (GRACE) satellite mission recorded temporal variations in the Earth’s gravity field, which are then converted to Total Water Storage Change (TWSC) fields representing an anomaly in the water mass stored in all three physical states, on and below the surface of the Earth. GRACE provided a first global observational record of water mass redistribution at spatial scales greater than 63000 km2. This limits their usability in regional hydrological applications. In this study, we implement a statistical downscaling approach that assimilates 0.5° × 0.5° water storage fields from the WaterGAP hydrology model (WGHM), precipitation fields from 3 models, evapotranspiration and runoff from 2 models, with GRACE data to obtain TWSC at a 0.5° × 0.5° grid. The downscaled product exploits dominant common statistical modes between all the hydrological datasets to improve the spatial resolution of GRACE. We also provide open access to scripts that researchers can use to produce downscaled TWSC fields with input observations and models of their own choice.
A novel causality-centrality-based method for the analysis of the impacts of air pollutants on PM2.5 concentrations in China
Authors: Wang Bocheng 
Published: March 2021

AbstractIn this paper, we analyzed the spatial and temporal causality and graph-based centrality relationship between air pollutants and PM2.5 concentrations in China from 2013 to 2017. NO2, SO2, CO and O3 were considered the main components of pollution that affected the health of people; thus, various joint regression models were built to reveal the causal direction from these individual pollutants to PM2.5 concentrations. In this causal centrality analysis, Beijing was the most important area in the Jing-Jin-Ji region because of its developed economy and large population. Pollutants in Beijing and peripheral cities were studied. The results showed that NO2 pollutants play a vital role in the PM2.5 concentrations in Beijing and its surrounding areas. An obvious causality direction and betweenness centrality were observed in the northern cities compared with others, demonstrating the fact that the more developed cities were most seriously polluted. Superior performance with causal centrality characteristics in the recognition of PM2.5 concentrations has been achieved.
Amikacin nebulization for the adjunctive therapy of gram-negative pneumonia in mechanically ventilated patients: a systematic review and meta-analysis of randomized controlled trials
Authors: Qin Jun-Ping , Huang Hui-Bin , Zhou Hua , Zhu Yuan , Xu Yuan , Du Bin 
Published: March 2021

AbstractTreatment of ventilated patients with gram-negative pneumonia (GNP) is often unsuccessful. We aimed to assess the efficacy and safety of nebulized amikacin (NA) as adjunctive therapy to systemic antibiotics in this patient population. PubMed, Embase, China national knowledge infrastructure, Wanfang, and the Cochrane database were searched for randomized controlled trials (RCTs) investigating the effect of NA as adjunctive therapy in ventilated adult patients with GNP. Heterogeneity was explored using subgroup analysis and sensitivity analysis. The Grading of recommendations assessment, development, and evaluation approach was used to assess the certainty of the evidence. Thirteen RCTs with 1733 adults were included. The pooled results showed NA had better microbiologic eradication (RR = 1.51, 95% CI 1.35 to 1.69, P < 0.0001) and improved clinical response (RR = 1.23; 95% CI 1.13 to 1.34; P < 0.0001) when compared with control. Meanwhile, overall mortality, pneumonia associated mortality, duration of mechanical ventilation, length of stay in ICU and change of clinical pneumonia infection scores were similar between NA and control groups. Additionally, NA did not add significant nephrotoxicity while could cause more bronchospasm. The use of NA adjunctive to systemic antibiotics therapy showed better benefits in ventilated patients with GNP. More well-designed RCTs are still needed to confirm our results.
Diquafosol tetrasodium elicits total cholesterol release from rabbit meibomian gland cells via P2Y2 purinergic receptor signalling
Authors: Endo Ken-ichi , Sakamoto Asuka , Fujisawa Koushi 
Published: March 2021

AbstractDiquafosol tetrasodium (DQS), a purinergic P2Y2 receptor agonist, stimulates secretion of both water and mucins from the conjunctiva into tears. Hence, DQS-containing eye drops have been approved as a therapeutic option for dry eye disease in some Asian countries, including Japan. Recent clinical reports state that instilling DQS-containing eye drops significantly increases the lipid layer thickness in tears. Therefore, we examined this compound’s direct actions on holocrine lipid-secreting meibomian gland cells and their function. Isolated meibomian gland cells (meibocytes) were procured from rabbits and cultivated in serum-free culture medium. Differentiated meibocytes with pioglitazone were used for the subsequent experiments. Intracellular Ca2+ signalling of the cells was dramatically elevated with DQS addition in a dose-dependent manner. This DQS-induced elevation was almost completely cancelled by the coexistence of the selective P2Y2 receptor antagonist AR-C118925XX. DQS treatment also facilitated total cholesterol (TC) release from cells into the medium. This effect of DQS on TC was suppressed significantly by the intracellular Ca2+ chelator BAPTA-AM as well as by AR-C118925XX. DNA fragmentation analysis revealed that DQS may have enhanced the apoptotic DNA fragmentation caused spontaneously by cells. Thus, DQS could stimulate meibocytes to release lipids through the P2Y2 receptor and possibly facilitate holocrine cell maturation.
Ultrafast excited state relaxation dynamics in a heteroleptic Ir(iii) complex, fac-Ir(ppy)2(ppz), revealed by femtosecond X-ray transient absorption spectroscopy
Authors: Choi Jungkweon , Ahn Mina , Lee Jae Hyuk , Ahn Doo-Sik , Ki Hosung , Oh Inhwan , Ahn Chi Woo , Choi Eun Hyuk , Lee Yunbeom , Lee Seonggon , Kim Jungmin , Cho Dae Won , Wee Kyung-Ryang , Ihee Hyotcherl 
Published: March 2021

The experimental and calculation results demonstrate that the 3MLppzCT state generated by the spin-forbidden transition rapidly relaxes to 3MLppyCT through internal conversion process with a time constant of ∼450 fs.