bluuebunny/crossref_metadata_2025_split huggingface dataset:
High glucose induced c-Met activation promotes aggressive phenotype and regulates expression of glucose metabolism genes in HCC cells
Authors: Topel Hande , Bağırsakçı Ezgi , Yılmaz Yeliz , Güneş Ayşim , Bağcı Gülsün , Çömez Dehan , Kahraman Erkan , Korhan Peyda , Atabey Neşe 
Published: May 2021

AbstractHepatocellular carcinoma (HCC) is strongly associated with metabolic dysregulations/deregulations and hyperglycemia is a common metabolic disturbance in metabolic diseases. Hyperglycemia is defined to promote epithelial to mesenchymal transition (EMT) of cancer cells in various cancers but its molecular contribution to HCC progression and aggressiveness is relatively unclear. In this study, we analyzed the molecular mechanisms behind the hyperglycemia-induced EMT in HCC cell lines. Here, we report that high glucose promotes EMT through activating c-Met receptor tyrosine kinase via promoting its ligand-independent homodimerization. c-Met activation is critical for high glucose induced acquisition of mesenchymal phenotype, survival under high glucose stress and reprogramming of cellular metabolism by modulating glucose metabolism gene expression to promote aggressiveness in HCC cells. The crucial role of c-Met in high glucose induced EMT and aggressiveness may be the potential link between metabolic syndrome-related hepatocarcinogenesis and/or HCC progression. Considering c-Met inhibition in hyperglycemic patients would be an important complementary strategy for therapy that favors sensitization of HCC cells to therapeutics.
Novel semi-automated fluorescence microscope imaging algorithm for monitoring IgG aggregates in serum
Authors: Sreenivasan Shravan , Sonawat Deepak , Mandal Shyamapada , Khare Kedar , Rathore Anurag S. 
Published: May 2021

AbstractAnalysis of therapeutic IgG aggregates in serum is a potential area of investigation as it can give deeper insights about the function, immunogenic issues and protein interaction associated with the aggregates. To overcome various complexities associated with the existing analytical techniques for analyzing aggregates in serum, a novel florescence microscopy-based image processing approach was developed. The monoclonal antibody (mAb) was tagged with a fluorescent dye, fluorescein isothiocyanate (FITC). Aggregates, generated by stirring, were spiked into serum and images were captured at various time points. After denoising, thresholding by weighted median, 1D Otsu, and 2D Otsu was attempted and a modified 2D Otsu, a new mode of thresholding, was developed. This thresholding method was found to be highly effective in removing noises and retaining analyte sizes. Out of 0–255, the optimized threshold value obtained for the images discussed in modified 2D Otsu was 9 while 2D Otsu’s overestimated values were 38 and 48. Other morphological operations were applied after thresholding and the area, perimeter, circularity, and radii of the aggregates in these images were calculated. The proposed algorithm offers an approach for analysis of aggregates in serum that is simpler to implement and is complementary to existing approaches.
Platelet derived growth factor receptor β (PDGFRβ) is a host receptor for the human malaria parasite adhesin TRAP
Authors: Steel Ryan W. J. , Vigdorovich Vladimir , Dambrauskas Nicholas , Wilder Brandon K. , Arredondo Silvia A. , Goswami Debashree , Kumar Sudhir , Carbonetti Sara , Swearingen Kristian E. , Nguyen Thao , Betz Will , Camargo Nelly , Fisher Bridget S. , Soden Jo , Thomas Helen , Freeth Jim , Moritz Robert L. , Noah Sather D. , Kappe Stefan H. I. 
Published: May 2021

AbstractFollowing their inoculation by the bite of an infected Anopheles mosquito, the malaria parasite sporozoite forms travel from the bite site in the skin into the bloodstream, which transports them to the liver. The thrombospondin-related anonymous protein (TRAP) is a type 1 transmembrane protein that is released from secretory organelles and relocalized on the sporozoite plasma membrane. TRAP is required for sporozoite motility and host infection, and its extracellular portion contains adhesive domains that are predicted to engage host receptors. Here, we identified the human platelet-derived growth factor receptor β (hPDGFRβ) as one such protein receptor. Deletion constructs showed that the von Willebrand factor type A and thrombospondin repeat domains of TRAP are both required for optimal binding to hPDGFRβ-expressing cells. We also demonstrate that this interaction is conserved in the human-infective parasite Plasmodium vivax, but not the rodent-infective parasite Plasmodium yoelii. We observed expression of hPDGFRβ mainly in cells associated with the vasculature suggesting that TRAP:hPDGFRβ interaction may play a role in the recognition of blood vessels by invading sporozoites.
Longitudinal effects of meditation on brain resting-state functional connectivity
Authors: Zhang Zongpai , Luh Wen-Ming , Duan Wenna , Zhou Grace D. , Weinschenk George , Anderson Adam K. , Dai Weiying 
Published: May 2021

AbstractChanges in brain resting-state functional connectivity (rsFC) were investigated using a longitudinal design by following a 2-month focused attention meditation (FAM) practice and analyzing their association with FAM practice time. Ten novice meditators were recruited from a university meditation course. Participants were scanned with a resting-state fMRI sequence with multi-echo EPI acquisition at baseline and at the 2-month follow-up. Total FAM practice time was calculated from the daily log of the participants. We observed significantly increased rsFC between the posterior cingulate cortex (PCC) and dorsal attention network (DAN), the right middle temporal (RMT) region and default mode network (DMN), the left and right superior parietal lobules (LSPL/RSPL) and DMN, and the LSPL/RSPL and DAN. Furthermore, the rsFC between the LSPL and medial prefrontal cortex was significantly associated with the FAM practice time. These results demonstrate increased connectivity within the DAN, between the DMN and DAN, and between the DMN and visual cortex. These findings demonstrate that FAM can enhance the brain connection among and within brain networks, especially DMN and DAN, indicating potential effect of FAM on fast switching between mind wandering and focused attention and maintaining attention once in the attentive state.
C1q/TNF-related protein-9 ameliorates hypoxia-induced pulmonary hypertension by regulating secretion of endothelin-1 and nitric oxide mediated by AMPK in rats
Authors: Jin Qiaoyan , Su Hui , Yang Rui , Tan Yanzhen , Li Buying , Yi Wei , Dong Qianqian , Zhang Haifeng , Xing Wenjuan , Sun Xin 
Published: May 2021

AbstractInjury/dysfunction of the endothelium of pulmonary arteries contributes to hypoxia-induced pulmonary hypertension (HPH). We investigated whether C1q/tumor necrosis factor-related protein-9 (CTRP9), a newly identified cardiovascular agent, has protective roles in the development of HPH. HPH was induced in adult male rats by chronic hypobaric hypoxia. CTRP9 overexpression by adeno-associated virus (AAV)-CTRP9 transfection attenuated the increases in right ventricular systolic pressure, right ventricular hypertrophy index, and pulmonary arterial remodeling of rats under hypoxia. Importantly, CTRP9 overexpression improved endothelium-dependent vasodilation in pulmonary arterioles in HPH rats. CTRP9 overexpression enhanced expression of phosphorylated 5′-adenosine monophosphate-activated protein kinase (p-AMPK) and phosphorylated endothelial nitric oxide synthase (p-eNOS), and reduced phosphorylated extracellular signal-regulated protein kinase (p-ERK1/2) expression in pulmonary microvascular endothelial cells (PMVECs) of HPH rats. In cultured PMVECs, CTRP9 not only preserved the decrease of AMPK and eNOS phosphorylation level and nitric oxide (NO) production induced by hypoxia, but also blocked the increase in hypoxia-induced ERK1/2 phosphorylation level and endothelin (ET)-1 production. Furthermore, the effects of CTRP9 were interrupted by inhibitors or knockdown of AMPK. CTRP9 enhances NO production and reduces ET-1 production by regulating AMPK activation. CTRP9 could be a target for HPH.
Neutrophil to lymphocyte ratio and fibrinogen values in predicting patients with type B aortic dissection
Authors: Li Shuangshuang , Yang Jin , Dong Jian , Guo Renle , Chang Sheng , Zhu Hongqiao , Li Zhaohui , Zhou Jian , Jing Zaiping 
Published: May 2021

AbstractThe aim of this study is to detect the diagnosis value of neutrophil lymphocyte ratio (NLR) and fibrinogen (FIB) in type B aortic dissection (TBAD) patients. This retrospective observation study consisted patients with TBAD, aortic aneurysm and physical examination between January 1, 2016 and December 31, 2019. Demographic and clinical information after the first admission were collected. Multivariate logistic regression analysis was performed to explore the correlational relationship between NLR, FIB and TBAD. Receiver Operating Characteristic Curve (ROC) was performed to evaluate the diagnostic implication of NLR and FIB in TBAD patients. Six hundred and six patients who were first diagnosed with TBAD were included. Control groups were 202 aortic aneurysm and 140 physical examination subjects. The level of NLR and FIB in aortic dissection patients was significantly higher than aortic aneurysm patients and healthy group (P < 0.001). According to the results of multivariate logistic regression analysis, NLR and FIB were independent risk factors of aortic dissection, and the odds ratio (OR) and 95% confidence interval (CI) value of NLR and FIB were 1.499 (1.126–1.738) and 1.914 (1.475–2.485), respectively. The area under the curve (AUC) was 0.836 of NLR and 0.756 of FIB. NLR and FIB showed high specificity, 89% and 83% respectively. This is the first study provided information on the diagnosis performance of NLR and FIB in TBAD patients. NLR and FIB showed high specificity, which may be a valuable tool for the diagnosis of TBAD.
Novel electronic biosensor for automated inoculum preparation to accelerate antimicrobial susceptibility testing
Authors: Putney Suzanne , Theiss Andrew H. , Rajan Nitin K. , Deak Eszter , Buie Creighton , Ngo Yvonne , Shah Hima , Yuan Victoria , Botbol-Ponte Elizabeth , Hoyos-Urias Adrian , Knopfmacher Oren , Hogan Catherine A. , Banaei Niaz , Herget Meike S. 
Published: May 2021

AbstractA key predictor of morbidity and mortality for patients with a bloodstream infection is time to appropriate antimicrobial therapy. Accelerating antimicrobial susceptibility testing from positive blood cultures is therefore key to improving patient outcomes, yet traditional laboratory approaches can require 2–4 days for actionable results. The eQUANT—a novel instrument utilizing electrical biosensors—produces a standardized inoculum equivalent to a 0.5 McFarland directly from positive blood cultures. This proof-of-concept study demonstrates that eQUANT inocula prepared from clinically significant species of Enterobacterales were comparable to 0.5 McF inocula generated from bacterial colonies in both CFU/ml concentration and performance in antimicrobial susceptibility testing, with ≥ 95% essential and categorical agreement for VITEK2 and disk diffusion. The eQUANT, combined with a rapid, direct from positive blood culture identification technique, can allow the clinical laboratory to begin antimicrobial susceptibility testing using a standardized inoculum approximately 2–3 h after a blood culture flags positive. This has the potential to improve clinical practice by accelerating conventional antimicrobial susceptibility testing and the resulting targeted antibiotic therapy.
Percolation networks inside 3D model of the mineralized collagen fibril
Authors: Bini Fabiano , Pica Andrada , Marinozzi Andrea , Marinozzi Franco 
Published: May 2021

AbstractBone is a hierarchical biological material, characterized at the nanoscale by a recurring structure mainly composed of apatite mineral and collagen, i.e. the mineralized collagen fibril (MCF). Although the architecture of the MCF was extensively investigated by experimental and computational studies, it still represents a topic of debate. In this work, we developed a 3D continuum model of the mineral phase in the framework of percolation theory, that describes the transition from isolated to spanning cluster of connected platelets. Using Monte Carlo technique, we computed overall 120 × 106 iterations and investigated the formation of spanning networks of apatite minerals. We computed the percolation probability for different mineral volume fractions characteristic of human bone tissue. The findings highlight that the percolation threshold occurs at lower volume fractions for spanning clusters in the width direction with respect to the critical mineral volume fractions that characterize the percolation transition in the thickness and length directions. The formation of spanning clusters of minerals represents a condition of instability for the MCF, as it could be the onset of a high susceptibility to fracture. The 3D computational model developed in this study provides new, complementary insights to the experimental investigations concerning human MCF.
Heparan sulfate proteoglycan glypican-1 and PECAM-1 cooperate in shear-induced endothelial nitric oxide production
Authors: Bartosch Anne Marie W. , Mathews Rick , Mahmoud Marwa M. , Cancel Limary M. , Haq Zahin S. , Tarbell John M. 
Published: May 2021

AbstractThis study aimed to clarify the role of glypican-1 and PECAM-1 in shear-induced nitric oxide production in endothelial cells. Atomic force microscopy pulling was used to apply force to glypican-1 and PECAM-1 on the surface of human umbilical vein endothelial cells and nitric oxide was measured using a fluorescent reporter dye. Glypican-1 pulling for 30 min stimulated nitric oxide production while PECAM-1 pulling did not. However, PECAM-1 downstream activation was necessary for the glypican-1 force-induced response. Glypican-1 knockout mice exhibited impaired flow-induced phosphorylation of eNOS without changes to PECAM-1 expression. A cooperation mechanism for the mechanotransduction of fluid shear stress to nitric oxide production was elucidated in which glypican-1 senses flow and phosphorylates PECAM-1 leading to endothelial nitric oxide synthase phosphorylation and nitric oxide production.
Novel regulation of renal gluconeogenesis by Atp6ap2 in response to high fat diet via PGC1-α/AKT-1 pathway
Authors: Akhtar Safia , Culver Silas A. , Siragy Helmy M. 
Published: May 2021

AbstractRecent studies suggested that renal gluconeogenesis is substantially stimulated in the kidney in presence of obesity. However, the mechanisms responsible for such stimulation are not well understood. Recently, our laboratory demonstrated that mice fed high fat diet (HFD) exhibited increase in renal Atp6ap2 [also known as (Pro)renin receptor] expression. We hypothesized that HFD upregulates renal gluconeogenesis via Atp6ap2-PGC-1α and AKT pathway. Using real-time polymerase chain reaction, western blot analysis and immunostaining, we evaluated renal expression of the Atp6ap2 and renal gluconeogenic enzymes, PEPCK and G6Pase, in wild type and inducible nephron specific Atp6ap2 knockout mice fed normal diet (ND, 12 kcal% fat) or a high-fat diet (HFD, 45 kcal% fat) for 8 weeks. Compared with ND, HFD mice had significantly higher body weight (23%) (P < 0.05), renal mRNA and protein expression of Atp6ap2 (39 and 35%), PEPCK (44 and 125%) and G6Pase (39 and 44%) respectively. In addition, compared to ND, HFD mice had increased renal protein expression of PGC-1α by 32% (P < 0.05) and downregulated AKT by 33% (P < 0.05) respectively in renal cortex. Atp6ap2-KO abrogated these changes in the mice fed HFD. In conclusion, we identified novel regulation of renal gluconeogenesis by Atp6ap2 in response to high fat diet via PGC1-α/AKT-1 pathway.
Changes in each retinal layer and ellipsoid zone recovery after full-thickness macular hole surgery
Authors: Lee Min-Woo , Kim Tae-Yeon , Song Yong-Yeon , Baek Seung-Kook , Lee Young-Hoon 
Published: May 2021

AbstractTo analyze the changes in each retinal layer and the recovery of the ellipsoid zone (EZ) after full-thickness macular hole (FTMH) surgery. Patients who underwent surgery for FTMH were included. Spectral-domain optical coherence tomography (SD-OCT) was performed preoperatively and postoperatively at 1, 3, 6, 9, and 12 months. A total of 32 eyes were enrolled. Ganglion cell layer, inner plexiform layer, and inner nuclear layer showed significant reductions over time after surgery (P = 0.020, P = 0.001, and P = 0.001, respectively), but were significantly thicker than those of fellow eyes at 12 months postoperatively. The average recovery duration of the external limiting membrane (ELM), outer nuclear layer (ONL), and EZ was 1.5, 2.1, and 6.1 months, respectively. Baseline best-corrected visual acuity (BCVA) (P = 0.003), minimum linear diameter (MLD) (P = 0.025), recovery of EZ (P = 0.008), and IRL thickness (P < 0.001) were significant factors associated with changes in the BCVA. Additionally, axial length (P < 0.001), MLD (P = 0.020), and IRL thickness (P = 0.001) showed significant results associated with EZ recovery. The IRL gradually became thinner after FTMH surgery but was still thicker than that of the fellow eye at 12 months postoperatively. The recovery of ELM and ONL may be a prerequisite for the EZ recovery. The BCVA change was affected by baseline BCVA, MLD, recovery of EZ, and IRL thickness. Additionally, axial length, MLD, and IRL thickness were significantly associated with EZ recovery.
A nomogram based on clinicopathological features and serological indicators predicting breast pathologic complete response of neoadjuvant chemotherapy in breast cancer
Authors: Li Yijun , Zhang Jian , Wang Bin , Zhang Huimin , He Jianjun , Wang Ke 
Published: May 2021

AbstractA single tumor marker is not enough to predict the breast pathologic complete response (bpCR) after neoadjuvant chemotherapy (NAC) in breast cancer patients. We aimed to establish a nomogram based on multiple clinicopathological features and routine serological indicators to predict bpCR after NAC in breast cancer patients. Data on clinical factors and laboratory indices of 130 breast cancer patients who underwent NAC and surgery in First Affiliated Hospital of Xi'an Jiaotong University from July 2017 to July 2019 were collected. Multivariable logistic regression analysis identified 11 independent indicators: body mass index, carbohydrate antigen 125, total protein, blood urea nitrogen, cystatin C, serum potassium, serum phosphorus, platelet distribution width, activated partial thromboplastin time, thrombin time, and hepatitis B surface antibodies. The nomogram was established based on these indicators. The 1000 bootstrap resampling internal verification calibration curve and the GiViTI calibration belt showed that the model was well calibrated. The Brier score of 0.095 indicated that the nomogram had a high accuracy. The area under the curve (AUC) of receiver operating characteristic (ROC) curve was 0.941 (95% confidence interval: 0.900–0.982) showed good discrimination of the model. In conclusion, this nomogram showed high accuracy and specificity and did not increase the economic burden of patients, thereby having a high clinical application value.
The FlhA linker mediates flagellar protein export switching during flagellar assembly
Authors: Inoue Yumi , Kinoshita Miki , Kida Mamoru , Takekawa Norihiro , Namba Keiichi , Imada Katsumi , Minamino Tohru 
Published: May 2021

AbstractThe flagellar protein export apparatus switches substrate specificity from hook-type to filament-type upon hook assembly completion, thereby initiating filament assembly at the hook tip. The C-terminal cytoplasmic domain of FlhA (FlhAC) serves as a docking platform for flagellar chaperones in complex with their cognate filament-type substrates. Interactions of the flexible linker of FlhA (FlhAL) with its nearest FlhAC subunit in the FlhAC ring is required for the substrate specificity switching. To address how FlhAL brings the order to flagellar assembly, we analyzed the flhA(E351A/W354A/D356A) ΔflgM mutant and found that this triple mutation in FlhAL increased the secretion level of hook protein by 5-fold, thereby increasing hook length. The crystal structure of FlhAC(E351A/D356A) showed that FlhAL bound to the chaperone-binding site of its neighboring subunit. We propose that the interaction of FlhAL with the chaperon-binding site of FlhAC suppresses filament-type protein export and facilitates hook-type protein export during hook assembly.
Multi-species and multi-tissue methylation clocks for age estimation in toothed whales and dolphins
Authors: Robeck Todd R. , Fei Zhe , Lu Ake T. , Haghani Amin , Jourdain Eve , Zoller Joseph A. , Li Caesar Z. , Steinman Karen J. , DiRocco Stacy , Schmitt Todd , Osborn Steve , Van Bonn Bill , Katsumata Etsuko , Mergl June , Almunia Javier , Rodriguez Magdalena , Haulena Martin , Dold Christopher , Horvath Steve 
Published: May 2021

AbstractThe development of a precise blood or skin tissue DNA Epigenetic Aging Clock for Odontocete (OEAC) would solve current age estimation inaccuracies for wild odontocetes. Therefore, we determined genome-wide DNA methylation profiles using a custom array (HorvathMammalMethyl40) across skin and blood samples (n = 446) from known age animals representing nine odontocete species within 4 phylogenetic families to identify age associated CG dinucleotides (CpGs). The top CpGs were used to create a cross-validated OEAC clock which was highly correlated for individuals (r = 0.94) and for unique species (median r = 0.93). Finally, we applied the OEAC for estimating the age and sex of 22 wild Norwegian killer whales. DNA methylation patterns of age associated CpGs are highly conserved across odontocetes. These similarities allowed us to develop an odontocete epigenetic aging clock (OEAC) which can be used for species conservation efforts by provide a mechanism for estimating the age of free ranging odontocetes from either blood or skin samples.
Droplet-based microfluidic platform for high-throughput screening of Streptomyces
Authors: Tu Ran , Zhang Yue , Hua Erbing , Bai Likuan , Huang Huamei , Yun Kaiyue , Wang Meng 
Published: May 2021

AbstractStreptomyces are one of the most important industrial microorganisms for the production of proteins and small-molecule drugs. Previously reported flow cytometry-based screening methods can only screen spores or protoplasts released from mycelium, which do not represent the filamentous stationary phase Streptomyces used in industrial cultivation. Here we show a droplet-based microfluidic platform to facilitate more relevant, reliable and rapid screening of Streptomyces mycelium, and achieved an enrichment ratio of up to 334.2. Using this platform, we rapidly characterized a series of native and heterologous constitutive promoters in Streptomyces lividans 66 in droplets, and efficiently screened out a set of engineered promoter variants with desired strengths from two synthetic promoter libraries. We also successfully screened out several hyperproducers of cellulases from a random S. lividans 66 mutant library, which had 69.2–111.4% greater cellulase production than the wild type. Our method provides a fast, simple, and powerful solution for the industrial engineering and screening of Streptomyces in more industry-relevant conditions.