bluuebunny/crossref_metadata_2025 huggingface dataset:
The ecological niche of native and invasive fish congeners in Texas streams: evidence from morphology, stable isotope analysis, and stomach contents analysis
Authors: Shepta Erin , Perkin Joshuah S. , Mayes Kevin B. , Schalk Christopher M. , Montana Carmen G
Published: August 2022

Freshwater invasions have occurred worldwide with significant ecological, evolutionary, and economic impacts on recipient ecosystems. Researchers now have access to a combination of approaches to better identify the potential ecological impacts on recipient communities. We used an integrative approach based on morphological traits, stomach contents, and stable isotope ratios (δ13C and δ15N) to examine multiple dimensions of the niche of native Texas cyprinodontids, Red River pupfish (Cyprinodon rubrofluviatilis) and plains killifish (Fundulus zebrinus), and their sympatric invasive congeners sheepshead minnow (C. variegates) and gulf killifish (F. grandis). We analyzed specimens from the Brazos River and Red River basins in Texas collected during multiple surveys. Because of their phylogenetic relatedness, we predicted high overlap in the feeding habits and habitat-use between native and invasive congeners. A principal component analysis performed on 24 morphological traits associated with habitat-use and feeding ecology suggested some overlap on trait space occupied by the two Cyprinodon species, but no overlap between the two Fundulus species. High overlap on dietary and isotopic niche space was observed between the native and invasive Cyprinodon and the Fundulus species. Values of δ13C and δ15N ratios revealed that the native and invasive Cyprinodon species occupied virtually identical isotopic niches, while two Fundulus species showed only slight differences. While species differed in their trait space, similarities in the feeding ecology between cyprinodontid congeners could lead to negative ecological interactions related to food resources. Our findings highlight the needs for continued monitoring of invasive cyprinodontids to prevent their spread into upstream reaches of the Brazos River to ensure conservation of native congeners.
Dynamic Network Curvature Analysis of Gene Expression Reveals Novel Potential Therapeutic Targets in Sarcoma
Authors: Tannenbaum Allen , Elkin Rena , Oh Jung Hun , Cruz Filemon Dela , Norton Larry , Deasy Joseph , Kung Andrew
Published: August 2022

To identify molecular targets that would be missed by more conventional methods of analysis, we applied a novel unsupervised method to cluster gene interactomes represented as networks in pediatric sarcoma. RNA-Seq data were mapped to protein- level interactomes to construct weighted networks that were then subjected to a non-Euclidean, multi-scale geometric approach centered on a discrete notion of curvature. This provides a measure of the functional association between genes in the context of their connectivity. In confirmation of the validity of this method, hierarchical clustering revealed the characteristic EWSR1-FLI1 fusion in Ewing sarcoma. Furthermore, assessing the effects of in silico edge perturbations and simulated gene knockouts as quantified by changes in curvature, we found non-trivial gene associations not previously identified.
Agonistic Tie2 antibody suppresses normal-to-tumor vascular transition in glioblastoma invading zone
Authors: Kim Injune , Lee Eunhyeong , Lee Eun-Ah , Kong Eunji , Chon Haemin , Park Cheon Ho , Park Beom Yong , Kang Nuri , Yoo Jin-San , Lee Hyun-Soo , Kim Hyung Seok , Park Sung-Hong , choi seung won , Vestweber Dietmar , Lee Jeong Ho , Kim Pilhan , Lee Weon Sup
Published: August 2022

Tumor progression is intimately associated with the vasculature, as tumor proliferation induces angiogenesis and tumor cells metastasize to distant organs via blood vessels. However, whether tumor invasion is associated with blood vessels remains unknown. As glioblastoma (GBM) is featured by aggressive invasion and vascular abnormalities, we characterized the onset of vascular remodeling in the diffusive tumor-infiltrating zone by establishing new spontaneous GBM models with robust invasion capacity. Normal brain vessels underwent a gradual transition to severely impaired tumor vessels at the GBM periphery over several days. Increasing vasodilation from the tumor periphery to tumor core was also found in human GBM. The levels of VEGF and VEGFR2 showed a spatial correlation with the extent of vascular abnormality spanning the tumor invading zone. Blockade of VEGFR2 suppressed vascular remodeling at the tumor periphery, confirming the role of VEGF-VEGFR2 signaling in invasion-associated vascular transition. As ANGPT2 was expressed only in a portion of the central tumor vessels, we developed a ligand-independent Tie2-activating antibody that can phosphorylate Tie2 in vivo. This agonistic Tie2 antibody effectively normalized the vasculature in both the tumor periphery and tumor center, similar to VEGFR2 blockade. Mechanistically, this antibody-based Tie2 activation induced VE-PTP-mediated VEGFR2 dephosphorylation in vivo. Thus, our study reveals that the normal-to-tumor vascular transition spatio-temporally associates with GBM invasion and may be controlled by Tie2 activation with a novel mechanism-of-action.
Regulation of inflammation-mediated endothelial to mesenchymal transition with Echinochrome A for improving myocardial dysfunction
Authors: Chang Woochul , Song Byeong-Wook , Kim Sejin , Kim Ran , Jeong Seongtae , Moon Hanbyeol , Kim Hojin , Vasileva Elena A , Mishchenko Natalia P , Fedoreyev Sergey A , Stonik Valentin A , Lee Min Young , Kim Jongmin , Kim Hyoung Kyu , Han Jin
Published: August 2022

Cardiovascular disease induced by myocardial ischemia is caused by excessive oxidative stress, which eventually leads to cell death and tissue damage. Endothelial–mesenchymal transition (EndMT) is a process by which endothelial cells (ECs) transition into mesenchymal cells (e.g., myofibroblasts and smooth muscle cells) and induce fibrosis of cells/tissues due to ischemic conditions. Previously, we reported that echinochrome A (EchA) derived from sea urchin shells can modulate cardiovascular disease by promoting anti-inflammatory and antioxidant activity; however, the mechanism underlying these effects was unclear. Hence, in this study, we investigated the role of EchA in EndMT process by treating human umbilical vein ECs (HUVECs) with TGF-β2 and IL-1β. We confirmed that EchA treatment in HUVECs reduces cell migration via non-Smad signaling pathways and generally modulates inflammatory and oxidative responses and mitochondrial dysfunction. Moreover, we developed an EndMT-induced myocardial infarction (MI) model to investigate the effect of EchA in vivo. After EchA was administered once a day for a total of 3 days, the histological and functional improvement of the myocardium was investigated to confirm the control of the transition to mesenchymal cells. We conclude that EchA negatively regulates early or inflammation-related EndMT and reduces myofibroblast proportion and fibrosis area, indicating it as a potential therapy for cardiac regeneration or cardioprotection from scar formation and cardiac fibrosis due to tissue granulation. Our findings encourage the study of marine bioactive compounds for the discovery of new therapeutics for cardiac recovery after ischemic injury.
Relational victimization, characterological self-blame, and adjustment in young children
Authors: Blakely-McClure Sarah J. , Ostrov Jamie M.
Published: August 2022

The associations between relational victimization, self-blame attributions, and internalizing problems in early childhood has not previously been examined. Using a sample of 116 preschool children, average age 44.05 months (SD = 4.23), multiple informants, multiple methods, and a longitudinal design, path analyses were conducted to explore the associations between relational victimization, self-blame attributions (Characterological Self-Blame[CSB] and Behavioral Self-Blame[BSB]), and maladjustment in early childhood. Concurrent significant associations were found between relational victimization and internalizing problems. The initial longitudinal models revealed some significant effects that were consistent with predictions. Importantly, follow-up tests decomposing internalizing problems, indicated that anxiety at Time 1 was positively and significantly associated with CSB at Time 2. Depression at Time1 was negatively and significantly associated with CSB at Time 2. Implications of this work are discussed.
Levosimendan inhibits disulfide tau oligomerization ameliorating tau pathology in TauP301L-BiFC mice
Authors: Kim Yun Kyung , Pae Ae Nim , Lim Sungsu , Shin Seulgi , Lee Ha Eun , Song Ji Yeon , Sung Yoonsik , Lee Gwan-Ho , Yu Byung-Yong , Aziz Hira , Lukianenko Nataliia , Kim Kyu Hyeon , Jeong Hyeanjeong , Lim Sang Min , Lee Jun-Seok , Ryu Hoon
Published: August 2022

Tau oligomers play critical roles in tau pathology, responsible for neuronal cell death and transmitting the disease in the brain. Accordingly, preventing tau oligomerization becomes an important therapeutic strategy to treat tauopathies including Alzheimer’s disease. However, progress has been slow due to difficulties of detecting tau oligomers in cellular context. Toward tau-targeted drug discovery, our group has developed a tau-BiFC platform to monitor and quantify tau oligomerization. By using the tau-BiFC platform, we screened FDA-approved & Passed PhaseI drug library, and identified levosimendan as a potent anti-tau agent inhibiting tau oligomerization. 14C-isotope labeling of levosimendan identified that levosimendan covalently bound to tau cysteines, directly inhibiting disulfide-linked tau oligomerization. In addition, levosimendan was able to disassemble tau oligomers into monomers, rescuing neurons from aggregation states. In comparison, the well-known anti-tau agents, methylene blue and LMTM, failed to protect neurons from tau-mediated toxicity, generating high-molecular-weight tau oligomers. Levosimendan displayed robust potency against tau oligomerization and rescued tauopathy-induced cognitive declines in TauP301L-BiFC mouse model. Our data present the potential of levosimendan as a disease-modifying drug for tauopathies.
Examining Antibiotic Prescribing and Urine Culture Testing for Urinary Tract Infections (UTIs) in a Primary Care Spinal Cord Injury (SCI) cohort
Authors: Senthinathan Arrani , Craven B. Catharine (Cathy) , Morris Andrew , Penner Melanie , Jaglal Susan
Published: August 2022

Study Design: A retrospective cohort study Objectives: To describe antibiotic prescribing and urine culture testing patterns for urinary tract infections (UTIs) in a primary care Spinal Cord Injury (SCI) cohort.Setting: A primary care electronic medical records (EMR) database in Ontario.Methods: Using linked EMR health administrative databases to identify urine culture and antibiotic prescriptions ordered in primary care for 432 individuals with SCI from January 1 ,2013 to December 31, 2015. Descriptive statistics were conducted to describe the SCI cohort, and physicians. Regression analyses were conducted to determine patient and physician factors associated with conducting a urine culture and class of antibiotic prescription. Results: The average annual number of antibiotic prescriptions for UTI for the SCI cohort during study period was 1.9. Urine cultures were conducted for 58.1% of antibiotic prescriptions. Fluroquinolones and nitrofurantoin were the most frequently prescribed antibiotics. Male physicians and international medical graduates were more likely to prescribe fluroquinolones than nitrofurantoin for UTIs. Early-career physicians were more likely to order a urine culture when prescribing an antibiotic. No patient characteristics were associated with obtaining a urine culture or antibiotic class prescription.Conclusion: Nearly 60% of antibiotic prescriptions for UTIs in the SCI population were associated with a urine culture. Only physician characteristics, not patient characteristics, were associated with whether or not a urine culture was conducted, and the class of antibiotic prescribed. Future research should aim to further understand physician factors with antibiotic prescribing and urine culture testing for UTIs in the SCI population.
HIV-1 infection of human tonsils activates CD4+ T cell oxidative phosphorylation and myeloid NLRP3 inflammasome activation
Authors: Freeman Tracey , Zhao Connie , Schrode Nadine , Tweel Benjamin , Fortune Trinisia , Schroff Sanjana , Beaumont Kristin , Swartz Talia
Published: August 2022

Human immunodeficiency virus type 1 (HIV-1) leads to a chronic, incurable infection that causes immune activation, resulting in chronic inflammation in people with HIV-1 (PWH) despite virologic suppression on antiretroviral therapy (ART). The mechanisms underlying this chronic inflammation are multifactorial, but significant literature supports the role of lymphoid structures as reservoirs for viral latency and centers of immune activation. A systematic analysis of the cell type-specific transcriptomic changes induced by HIV-1 infection in lymphoid tissue has not been conducted. Human tonsil explants from four distinct donors were infected with HIV-1 ex vivo. Single-cell RNA sequencing (scRNA Seq) was performed to evaluate the represented cell types and the impact of infection, including differential gene expression, and associated inflammatory signaling pathways. Most of the cells (80%) are lymphocytes with nearly equivalent representation from T (38%) and B (42%) lymphocytes. We also identify smaller populations of NK, epithelial, and myeloid cells. CD4+ T cells demonstrated the highest levels of HIV-1 transcript expression. Highly infected CD4+ T cells also exhibited increased expression of genes involved in the respiratory electron transport pathway. Cells in the myeloid compartment that expressed low levels of HIV-1 transcript demonstrated increased expression of genes involved in the NLRP3 inflammasome pathway, suggesting that these cells may play a “bystander” role in HIV-associated inflammatory pathogenesis. We propose a model in which HIV-1-infected CD4+ T cells activate oxidative phosphorylation pathways, resulting in excess ATP efflux. Bystander myeloid cells may sense the resulting extracellular ATP, thereby triggering NLRP3 inflammasome activation, proinflammatory signaling pathways, and pyroptotic cell death. These observations support important mechanistic understanding to drive the development of therapeutic and care strategies to eradicate disease in PWH.
Stochastic convergence of ecological footprint: new insights from a unit root test based on smooth transitions and nonlinear adjustment
Authors: Alper Ali Eren , Alper Findik Ozlem , Cil Almila Burgac , Iscan Erhan , Eren Ahmet Arif
Published: August 2022

The ecological footprint has currently become a highly popular environmental performance indicator. It provides the basis for setting goals, identifying options for action, and tracking progress toward stated goals. Because the examination of the existence of convergence is important for the climate change protection of the earth, the convergence of ecological footprint and its subcomponents are a major concern for scholars and policymakers.To this end, the aim of this study is to investigate the stochastic convergence of ecological footprint and its subcomponents. We employ the recently developed Hepsag (2021) unit root test that allow nonlinearity and smooth structural change simultaneously to study stochastic convergence in per capita ecological footprint over the period 1961–20118 for the most polluting countries. The results provide mixed evidence of the presence of stochastic convergence in conventional unit root tests such as ADF, KPSS and Fourier KPSS. According to the Hepsag (2021) unit root test results for all countries, built-up land footprint converges except Australia, Malaysia, Poland, and Turkey. Carbon footprint converges for Indonesia, Malaysia, Mexico, South Africa, Thailand, Turkey, the UK, and the USA. Cropland footprint converges for Australia, Canada, China, France, Indonesia, Italy, Japan, Korea, Malaysia, Mexico, Poland, South Africa, the UK, and Vietnam. Fishing grounds footprint converges in Brazil, France, Germany, Indonesia, Italy, Mexico, South Africa, and Vietnam. Forest product footprint converges in Australia, Canada, France, Germany, India, Korea, Mexico, Poland, Turkey, and Vietnam. Grazing land footprint converges in Canada, France, India, Indonesia, Japan, Korea, Poland, South Africa, Thailand, and Vietnam. And lastly, the total ecological footprint converges in Canada, France, Korea, Malaysia, Mexico, South Africa, the UK, and the USA.
Overexpressed cold inducible RNA-binding protein improves cell viability and EGF expression in glial cells
Authors: Liu Aijun , Li Shouchun , Zhang Haitao , Jiao Yongcheng , Kong Haibo , Zhang Zhiwen
Published: August 2022

Background: Cold inducible RNA-binding protein (CIRP) is key protein in the hypothermic therapy. Highly expressed CIRP exerts a neuroprotective effect on neurons. The aim of this study is to provide the evidence of the protective effects of CIRP on the glial cells and try to explore the underlying mechanisms. Results: The results of this study demonstrated that the cell viability of the glial cells with CIRP overexpression was increased significantly compared to the control cells. With CIRP overexpression, the EGF mRNA expression was found increasing significantly and the mRNA expression of BDNF, bcl-2, VEGF and NGF were not upregulated compared to the control. EGF and CIRP co-expression was demonstrated on the glial cells. With CIRP expression, EGF expression on the glial cells was increased statistically compared to the control.Conclusions: CIRP overexpression increases the cell viability of the glial cells, exerting a neuroprotective effect. EGF expression is activated on the glial cells with CIRP overexpression, implying a pathway of CIRP neuroprotection via EGF activation.
Salt-inducible kinase 1-CREB-regulated transcription coactivator 1 signalling in the paraventricular nucleus of the hypothalamus plays a role in depression by regulating the hypothalamic–pituitary–adrenal axis
Authors: Jiang Bo , Wang Yuan , Liu Ling , Gu Jiang-Hong , Wang Cheng-Niu , Guan Wei , Liu Yue , Tang Wen-Qian , Ji Chun-Hui , Chen Yan-Mei , Huang Jie , Li Wei-Yu , Shi Tian-Shun , Chen Wei-Jia , Zhu Bao-Lun
Published: August 2022

Elucidating the molecular mechanism underlying the hyperactivity of the hypothalamic–pituitary–adrenal axis during chronic stress is critical for understanding depression and treating depression. The secretion of corticotropin-releasing hormone (CRH) from neurons in the paraventricular nucleus (PVN) of the hypothalamus is controlled by salt-inducible kinases (SIKs) and CREB-regulated transcription co-activators (CRTCs). We hypothesized that the SIK-CRTC system in the PVN might contribute to the pathogenesis of depression. Thus, the present study employed chronic social defeat stress (CSDS) and chronic unpredictable mild stress (CUMS) models of depression, various behavioral tests, virus-mediated gene transfer, enzyme linked immunosorbent assay, western blotting, co-immunoprecipitation, quantitative real-time reverse transcription polymerase chain reaction, and immunofluorescence to investigate this connection. Our results revealed that both CSDS and CUMS induced significant changes in SIK1-CRTC1 signaling in PVN neurons. Both genetic knockdown of SIK1 and genetic overexpression of CRTC1 in the PVN simulated chronic stress, producing a depression-like phenotype in naïve mice, and the CRTC1-CREB-CRH pathway mediates the pro-depressant actions induced by SIK1 knockdown in the PVN. In contrast, both genetic overexpression of SIK1 and genetic knockdown of CRTC1 in the PVN protected against CSDS and CUMS, leading to antidepressant-like effects in mice. Moreover, stereotactic infusion of TAT-SIK1 into the PVN also produced beneficial effects against chronic stress. Furthermore, the SIK1-CRTC1 system in the PVN played a role in the antidepressant actions of fluoxetine, paroxetine, venlafaxine, and duloxetine. Collectively, SIK1 and CRTC1 in PVN neurons are closely involved in depression neurobiology, and they could be viable targets for novel antidepressants.
Integrin beta1 (ITGB1) as a prognostic marker in esophageal adenocarcinoma
Authors: Damanakis Alexander I. , Wahler Isabell , Fuchs Hans , Löser Heike , Schröder Wolfgang , Zander Thomas , Chon Seung , Bruns Christiane , Quaas Alexander , Gebauer Florian
Published: August 2022

Background: Today, individual prognosis in patients with adenocarcinoma of the esophagus (EAC) is based on post-surgical TNM staging and valid biomarkers are still not implemented. Integrin beta1 (ITGB1) is widely expressed in epithelial cells and promotes cell adhesion and growth. Its impact on tumor progression was described for different tumor entities before, data on its function as biomarker in EAC has not been described. Aim of the study is to evaluate the expression level of ITGB1 in a very large collective of EAC and its impact on individual patients´ prognosis.Methods: 685 patients with esophageal adenocarcinoma were analyzed immunohistochemically for ITGB1. The data was correlated with long term outcome, clinical, pathological and molecular data (TP53, HER2/neu, c-myc, GATA6, PIK3CA and KRAS).Results: Of 640 patients to be analyzed, 127 (19.8%) showed expression of ITGB1. ITGB1 expression was associated with lymph node metastasis, expression of integrin alphaV and KRAS mutation status. Patients with high ITGB1 expression showed impaired overall survival (22.5 months (95%CI: 15.3 – 29.7 months), vs. 34.1 months (95%CI: 25.3 – 42.4 months, P = 0.024). This effect was particularly evident in the group of patients undergoing primary surgery without prior neoadjuvant therapy (10.2 months (95%CI 1.9 – 41.7 months) vs. 31.4 months (95%CI: 21.1 – 144.2 months, p = 0.008). ITGB1 acts here as an independent prognostic marker in multivariable analysis.Conclusion: We demonstrate for the first time the prognostic significance of ITGB1 expression in a large EAC patient population. ITGB1 apparently influences tumor progression in EAC and is associated with a poor prognosis.
Comparative site-specific N-glycoproteome analysis reveals aberrant N-glycosylation and
gives new insights into mannose-6-phosphate pathway in cancer
Authors: Chen Minyong , Assis Diego , Benet Matthieu , McClung Colleen , Gordon Elizabeth , Ghose Shourjo , Dupard Steven , Willetts Matthew , Taron Christopher , Samuelson James
Published: August 2022

N-glycosylation is implicated in cancers and aberrant N-glycosylation is recognized as a hallmark of cancer. Here, we mapped and compared the site-specific N-glycoproteomes of colon cancer HCT116 cells and isogenic non-tumorigenic DNMT1/3b double knockout (DKO1) cells using Fbs1-GYR N-glycopeptide enrichment technology and trapped ion mobility spectrometry. Many significant changes in site-specific N-glycosylation were revealed, providing a molecular basis for further elucidation of the role of N-glycosylation in protein function. HCT116 cells display hypersialylation especially in cell surface membrane proteins. Both HCT116 and DKO1 show an abundance of paucimannose and 80% of paucimannose-rich proteins are annotated to reside in exosomes. The most striking N-glycosylation alteration was the degree of mannose-6-phosphate (M6P) modification. N-glycoproteomic analyses revealed that HCT116 displays hyper-M6P modification, which was orthogonally validated by M6P immunodetection. Significant observed differences in N-glycosylation patterns of the major M6P receptor, CI-MPR in HCT116 and DKO1 may contribute to the hyper-M6P phenotype of HCT116 cells. This comparative site-specific N-glycoproteome analysis provides a pool of potential N-glycosylation-related cancer biomarkers, but also gives new insights into the M6P pathway in cancer.
The effect of cycles of genomic selection on the wheat (T. aestivum) genome
Authors: Blanco Nelly Arguello , Sneller Clay
Published: August 2022

Genomic selection (GS) is widely used in plant breeders to shorten breeding cycles. Our objective was to assess the impact of rapid cycling GS on the wheat genome We used 3927 markers to genotype a training population (YTP) and individuals from five cycles (YC1-YC5) of GS for grain yield. We assessed changes of allele frequency, genetic distance, population structure, and linkage disequilibrium (LD). We found 27.3% of all markers had a significant allele frequency change by YC5, 18% experienced a significant change attributed to selection, and 9.3% had a significant change due to either drift or selection. A total of 725 of 3927 markers were fixed by YC5 with selection fixing 7.3% of the 725 markers. The genetic distance between cycles increased over time. The Fst value of 0.224 between YTP and YC5 indicates their relationship was low. The correlation between LD matrices and the number of LD blocks decreased over time. Overall, we found reduction in genetic diversity, increased genetic differentiation of cycles from the training population, and restructuring of the LD patterns over cycles. The accuracy of GS depends on the genomic similarity of the training population and the prediction populations. Our results show that similarity can decline rapidly over cycles of GS and seriously compromise the predictive ability of the YTP-based model. Our results support implementing a GS scheme where the training and prediction populations co-evolve instead of the use of a static training population.
Subjective Feelings associated with Expectations and Rewards during Risky Decision-making in Impulse Control Disorder
Authors: Liebenow Brittany , Jiang Angela , DiMarco Emily , Sands Lester , Moya-Mendez Mary , Laxton Adrian , Siddiqui Mustafa , Haq Ihtsham , Kishida Kenneth
Published: August 2022

Impulse Control Disorder (ICD) in Parkinson’s disease is a behavioral addiction induced by dopaminergic therapies, but otherwise unclear cognitive etiology. The current study investigates the influence of objective reward processing variables, dopaminergic therapy, and risky decision-making on ‘subjective feelings’ in patients with versus without ICD. Patients with (n = 18) and without (n = 12) a history of ICD secondary to Parkinson’s disease performed a risky decision-making task (on and off standard-of-care dopaminergic therapies). During the task, participants choose a ‘gamble’ or a ‘certain reward’ and report how they feel about decision outcomes. The subjective feeling of ‘pleasure’ is driven by different aspects of reward processing in patients with, versus without, a history of ICD. While off-medication, expectations about risky-decisions have a negative influence on subjective feelings in patients with a history of ICD versus a positive influence in patients without ICD. While on-medication, the influence of reward processing variables and recent experience on modulating subjective feelings in both patient groups are altered; patients with ICD become more emotionally reactive, whereas patients without ICD become less emotionally reactive. Computational modeling of risky decision-making behavior reveals latent factors that drive subjective feelings and risky behaviors in patients with versus without a history of ICD. Group differences are observed in off-medication states. Changes are induced in both groups with medication suggesting ICD-related decision-making may be driven by mechanisms associated with emotion regulation and that heightened dopaminergic processes may induce more reactive, less stable, emotion regulation in patients predisposed to developing ICD.
Geometry in CIELAB color space for protonation of pH indicators
Authors: Suzuki Takayuki , Kitano Karen , Ito Chihiro , Yamaguchi Tomohiro
Published: August 2022

Ultraviolet-visible spectroscopy provides color information on organic compounds during chemical reactions. Absorption spectra of a pH indicator during protonation show absorption bands from electronic transitions based on molecular structure. Information from the bands including the wavelength of maximum absorption and calculated molar extinction coefficient can provide specific parameters for the reactant (the indicator) and the product (the protonated indicator). However, these parameters never directly present what chemical reaction is occurring, which is typically only determined after identification of the compounds with other characterization methods. Here, we show that a geometric object, which was built out of the loci of chromaticity points for a polymer pH-indicator in CIELAB color space, indicates that the reaction is protonation. The object contains information about species, i.e., the pH-indicating portion and its protonated form. Each locus for different initial concentrations was a line segment, which corresponded to the protonation process. The segments for a polymer pH indicator with azobenzene as the pH-indicating dye portion at different initial concentrations created a planar triangle in CIELAB color space. For another polymer pH indicator of nitrophenol, the geometric space was a half line. The corresponding geometric equations may be specific to protonation including information about the chemical species.
C5L2 modulates BDNF production in human dental pulp stem cells via p38α pathway under LPS-induced inflammation
Authors: Irfan Muhammad , Chung Seung
Published: August 2022

Tissue injury affects nerve fibers and triggers an immune response, leading to inflammation. The complement system gets activated during inflammatory conditions and has been reported to be involved in the regeneration process. We have demonstrated that the C5a receptor (C5aR) has crucial roles in regeneration and healing processes including nerve sprouting and hard tissue formation. Another C5a-like 2 receptor (C5L2) has been cloned which is still considered controversial due to limited studies. We previously established that C5L2 regulates BDNF secretion in pulp fibroblasts. However, there is no study available on human dental pulp stem cells (DPSCs), especially in the inflammatory context. Stem cell therapy is an incipient technique to treat and prevent several diseases, while DPSCs are an emerging option to be considered due to their great ability to differentiate into a variety of cells and secrete nerve regeneration factors. Here, we demonstrated that C5L2 modulates brain-derived neurotropic factor (BDNF) secretion in DPSCs. Our results stated that C5L2 silencing through siRNA can increase the BDNF production which could accelerate the nerve regeneration process. Moreover, stimulation with lipopolysaccharide (LPS) enhanced BDNF production in C5L2 silenced DPSCs. Finally, we quantified BDNF secretion in supernatant and cell lysates using ELISA. Our results showed enhanced BDNF production in C5L2 silenced DPSCs and hampered by the p38MAPKα inhibitor. Taken together, our data reveal that C5L2 modulates BDNF production in DPSCs via the p38MAPKα pathway.
Metoprolol Exhibits Discrete Pharmacokinetics Using Various Sites of Sample Collection after Single Oral Dose Administration of Metoprolol Tartrate in SD Rats
Authors: Yesh Yeshwant Singh , Tiwari Sudhir K Tiwari , Prat Pratima Srivastava , Deepti Deepti Sahu , Ravi Ravi A Reddy , giri Giridhar Bilagi , Theertha Theertha Thykandy
Published: August 2022

The aim of the study was to investigate the influences of various routes of sampling on the pharmacokinetics profile metoprolol after single oral dose administration of metoprolol tartrate in rats. For this single dose parallel studies were conducted in SD rats at 5 mg/kg of metoprolol tartrate. In our investigation, significant differences were observed in the plasma PK profile of metoprolol using various routes of sample collection. The mean peak plasma metoprolol concentration obtained from jugular (Cmax; 170.0 ng/mL) and saphenous (Cmax; 113.2 ng/mL) routes were comparable. Similarly, retro-orbital route Cmax (50.0 ng/mL) was comparable with Cmax (76.2 ng/mL) of femoral route. In contrast, the Cmax (39.3 ng/mL) obtained from tail vein sampling route was significantly different (p ≤ 0.05) from all other sampling sites. The Cmax obtained from tail vein sampling site was approximately 2–4 folds less compared to other routes of sampling except for retro-orbital sampling site. Corresponding differences were also observed for other PK parameters. It was concluded that the sampling sites have profound impact on the PK parameters of metoprolol after single dose oral administration in rats.
Molecular surveillance of dihydroartemisinin-piperaquine resistance in northwestern Thailand
Authors: Win Khine Nwe , Manopwisedjaroen Khajohnpong , Phumchuea Kanit , Suansomjit Chayanut , Chotivanich Kesinee , Lawpoolsri Saranath , Cui Liwang , Sattabongkot Jetsumon , Nguitragool Wang
Published: August 2022

Background: Dihydroartemisinin-piperaquine (DHA-PPQ) combination therapy is the current first-line treatment for Plasmodium falciparum malaria in Thailand. Since its introduction in 2015, resistance to this drug combination has emerged in the eastern part of the Greater Mekong Subregion including the eastern part of Thailand near Cambodia. Our aim is to assess whether the resistance genotypes have arisen the western part of country.Methods: Fifty-seven P. falciparum-infected blood samples were collected in Tak province of northwestern Thailand between 2013 and 2019. Resistance to DHA was examined through the single nucleotide polymorphisms (SNPs) of kelch13. PPQ resistance was examined through the copy number plasmepsin-2 and the SNPs of Pfcrt.Results:Among the samples whose kelch13 were successfully sequenced, approximately half (31/55; 56%) had mutation associated with artemisinin resistance, including G533S (23/55; 42%), C580Y (6/55; 11%), and G538V (2/55; 4%). During the study period, G533S mutation appeared and increased from 20% (4/20) in 2014 to 100% (9/9) in 2019. No plasmepsin-2 gene amplification was observed, but one sample (1/54) had the Pfcrt F145I mutation previously implicated in PPQ resistance.Conclusions: Kelch13 mutation was common in Tak Province in 2013-2019. A new mutation G533S emerged in 2014 and rose to dominance, possibly fixation, in 2019. PPQ resistance marker Pfcrt F145I was also detected in 2019. Continued surveillance of treatment efficacy and drug resistance markers is warranted.
Deciphering the involvement of the Hippo pathway co-regulators, YAP/TAZ in invadopodia formation and matrix degradation
Authors: Venghateri Jubina , Dassa Bareket , Morgenstern David , Shreberk-Shaked Michal , Oren Moshe , Geiger Benjamin
Published: August 2022

Invadopodia are adhesive, actin-rich protrusions formed by metastatic cancer cells that degrade the extracellular matrix and facilitate invasion. They support the metastatic cascade by a spatially and temporally coordinated process whereby invading cells bind to the matrix, degrade it by specific metalloproteinases, and mechanically penetrate diverse tissue barriers by forming actin-rich extensions. However, despite the apparent involvement of invadopodia in the metastatic process, the molecular mechanisms that regulate invadopodia formation and function are still largely unclear. In this study, we have explored the involvement of the key Hippo pathway co-regulators, namely YAP, and TAZ, in invadopodia formation and matrix degradation. Towards that goal, we tested the effect of depletion of YAP, TAZ, or both on invadopodia formation and activity in multiple human cancer cell lines. We report that knockdown of YAP and TAZ or their inhibition by verteporfin induces a significant elevation in matrix degradation and invadopodia formation in several cancer cell lines. Conversely, overexpression of these proteins strongly suppresses invadopodia formation and matrix degradation. Proteomic and transcriptomic profiling of MDA-MB-231 cells, following co-knockdown of YAP and TAZ, revealed a significant change in the levels of key invadopodia-associated proteins, including the crucial proteins Tks5 and MT1-MMP (MMP14). Collectively, our findings show that YAP and TAZ act as negative regulators of invadopodia formation in diverse cancer lines, most likely by reducing the levels of essential invadopodia components. Dissecting the molecular mechanisms of invadopodia formation in cancer invasion may eventually reveal novel targets for therapeutic applications against invasive cancer.
Tracing the century-long evolution of microplastics deposited in cold seep
Authors: Feng Jing-Chun , Li Can-Rong , Tang Li , Wu Xiao-Nan , Wang Yi , Yang Zhifeng , Yuan Weiyu , Sun Liwei , Hu Weiqiang , Zhang Si
Published: August 2022

Microplastic (MP) pollution is one of the greatest threats to marine ecosystems. The deep sea is regarded as a hotspot for MP accumulation, but how do deposited MPs evolve from a long-term perspective? In particular, the occurrence features of MPs in cold seeps, which are characterized by methane-rich fluid seepage fueling one of the richest ecosystems on the seafloor, are unclear. Here, we demonstrated how MPs have been deposited in the Haima cold seep since the invention of plastics. We found that the burial rate of MPs exponentially increased since the massive global use of plastics in the 1930s, and this cold seep accommodates more MPs than do coastal areas. Upwelling fluid seepage facilitated the fragmentation and degradation behaviors of MPs. More MP-degrading microorganism populations and functional genes were discovered in methane seepage areas. Our findings illuminated the need to determine fundamental strategies for sustainable marine plastic pollution mitigation in the natural deep-sea environment.
The effect of shame on prosocial behavior toward a stranger
Authors: Li Saiqi , Wang Liusheng
Published: August 2022

Background: This study aimed to examine the effect of different types of shame on prosocial behavior to different help-seekers. Methods: A total of 120 participants were randomly assigned to a neutral mood condition, a public shame or a private shame conditions. Results: All participants rated their willingness to help a benefactor and a stranger in an everyday helping situation and a money-donating situation after emotion-inducement. The study found a higher willingness of participants in public shame group to help strangers than those in neutral mood and private shame groups. Conclusion: These findings support a facilitation effect of public shame on prosocial behavior toward strangers, indicating an effect of restoring motive of shame on social interaction. The results are further discussed in light of functionalism of shame.
Andrographolide exerts anti-respiratory syncytial virus activity by up-regulating heme oxygenase-1 independent of interferon responses in human airway epithelial cells
Authors: Che Siyi , Zhou Na , Liu Ying , Xie Jun , Liu Enmei
Published: August 2022

Background: Respiratory syncytial virus (RSV), the leading cause of mortality and morbidity in children under the age of five, is still lacking in safe and effective vaccines and antiviral agents for clinical use. Andrographolide exerts antiviral functions against a variety of viruses, but whether (and how) it exerts antiviral effects on RSV remains unclear.Methods and results: In vitro RSV infection models using A549 and 16HBE cell lines were established, and the effect of andrographolide on RSV was analyzed via RSV N gene load and proinflammatory levels. The RNA transcriptome was sequenced and data were analyzed by R software. Lentivirus was transfected to knockdown the expression of HO-1. Results showed andrographolide suppressed RSV replication and attenuated subsequent inflammation. RNA sequencing indicated that the hub gene heme oxygenase-1 (HO-1) may play a pivotal role in the anti-RSV effects of andrographolide. Furthermore, results verified that andrographolide exert antiviral effects against RSV partially by inducing HO-1, but did not activate the antiviral interferon response. Conclusion: Our findings demonstrated that andrographolide exerted anti-RSV activity by up-regulating HO-1 in human airway epithelial cells, which may provide novel insights into potential therapeutic targets and drug repurposing in RSV infection.
Anti-diabetic and anti-obesity activity of Caralluma adscendens var. gracilis and Caralluma pauciflora
Authors: Mopuri Ramgopal , Dowlathabad Muralidhara Rao , Kommidi Devendar Reddy , Erukainure Ochuko L. , Rao A.V.N. Appa , Rao G. Venkateshwer , Islam Md. Shahidul
Published: August 2022

The plants fractions of Caralluma adscendens var. gracilis and Caralluma pauciflora were evaluated for their total phenolic content in relation to their antioxidant activity and inhibitory effect of starch and lipids digestive enzymes. Among all fractions of C. adscendens var. gracilis and C. pauciflora, diethyl ether fractions showed highest phenolic content (36.23 ± 1.51 mg of GAE g− 1 DW, 28.21 ± 3.61 mg of GAE g− 1 DW), DPPH radical scavenging activity (27.96 ± 3.45 µg ml− 1 and 37.23 ± 0.92 µg ml− 1), inhibition of α-glucosidase (59.13 ± 1.31 µg ml− 1 and 73.03 ± 2.04 µg ml− 1), α-amylase (78.1 ± 3.47 µg ml− 1 110.5 ± 4.1µg ml− 1) and pancreatic lipase (41.91 ± 3.51 µg ml− 1 and 49.12 ± 3.89 µg ml− 1) compared to butanone and n-butanol fractions which showed little or no significant activities compared to standards. To the best of our knowledge, the present study provides the first evidence that these two plants (C. adscendens var. gracilis and C. pauciflora) are potent inhibitors of key enzymes in type 2 diabetes and obesity studies in vitro.
3-Tesla Magnetic Resonance Imaging as an Additional Radiographic Decision Aid for Oxford Unicompartmental Knee Arthroplasty Patient Selection
Authors: Cheng Chieh-Ming , Hsu Kao-Yao , Lai Ying-Chieh , Ho Chin-Shan , Yang Cheng-Pang , Chen Yi-Jou , Chiu Chih-Hao
Published: August 2022

Background: The indications for Oxford unicompartmental knee arthroplasty (UKA) have been investigated for decades. The use of radiological decision aids for Oxford UKA is widespread; however, recent evidence suggests that there is a high false-negative rate. The 3-Tesla (3T) magnetic resonance imaging (MRI) system is more accurate than the 1.5T MRI system and may perform even better with Stage III and IV osteoarthritis. Here, we investigated the relationship between MRI findings and patient-reported outcomes following Oxford UKA. Methods: Medical records were reviewed retrospectively for 94 patients (101 knees) receiving Oxford UKA. All patients had a preoperative 3T MRI scan, which identified full-thickness cartilage loss. Evidence of bone-on-bone lesions from plain X-ray, bone marrow edema, and medial meniscus root tear was also recorded. Clinical outcomes were assessed using the Oxford knee score (OKS), Tegner Lysholm knee scoring system (TLKSS), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) six months postoperatively. Results: We reviewed 94 patients (101 knees, 30 in male patients and 71 in female patients) with full-thickness cartilage loss on 3T MRI. There were no significant differences in the TLKSS, OKS, or WOMAC between groups with and without bone-on-bone lesions, bone marrow edema, or medial meniscus root tear six months postsurgery. Conclusion: The 3T MRI system is an applicable radiographical decision aid for Oxford UKA patient selection. Full-thickness cartilage loss on 3T MRI is sufficient for identifying Oxford UKA beneficiaries, regardless of bone-on-bone lesions, bone marrow edema, or medial meniscus root tear
Prognostic and Therapeutic Value of NK1R: Correlation between Function in Immune Infiltration and Expression in Tumor Microenvironment
Authors: Li Mingyu , Zhang Shunuo , Ma Hao , Zhang Yixin , Min Peiru
Published: August 2022

Background: NK1R is involved in the pathogenesis of inflammation. Although the function of NK1R in several types of cancer has been confirmed, relationship between the function of NK1R in inflammation and NK1R expression in tumor microenvironment is still absent, and the detailed immune mechanism remains unknown. Methods: We took advantage of TCGA, TARGET, GTEx, and other open access data to conduct pan-cancer analysis including differential expression, prognostic signature, gene set enrichment and tumor immunity in R. Results: NK1R was significantly up-regulated in 7 tumors and down-regulated in 23 tumors and possessed a strong correlation with clinical prognosis. Upregulated NK1R was related to the immune-related process and pathways. The positive correlation between NK1R expression and enhancement of RNA modification as well as immune regulation in most tumors indicated NK1R could function by up-regulating the modification and regulatory genes. Moreover, NK1R could improve the immune infiltration in most tumors, but reduce that in GBMLGG and LGG. Conclusions: NK1R regulated tumor microenvironment by facilitating the inflammation and subsequent immune response in tumor and stromal cells. The immunological function of NK1R significantly showed in most types of tumors, involved in oncogenesis and prognosis. Our findings revealed the potential of NK1R to be a survival indicator and therapy target.
CATCH: Chasing All Transients Constellation Hunters Space Mission
Authors: Li Panping , Yin Qian-Qing , Li Zhengwei , Tao Lian , Wen Xiangyang , Zhang Shuang-Nan , Qi Liqiang , Zhang Juan , Zhao Donghua , Li Dalin , Yu Xizheng , Bu Qingcui , Chen Wen , Chen Yupeng , Huang Yiming , Huang Yue , Jin Ge , Li Gang , Liu Hongbang , Liu Xiaojing , Ma Ruican , Peng Wenxi , Tang Ruijing , Wang Yusa , Xiao Jingyu , Xiong Shaolin , Yang Sheng , Yang Yanji , Zhang Chen , Zhang Tianchong , Zhang Xuan , Zhao Haisheng , Zhao Kang , Zhao Qingchang , Zhao Shujie , Zhou Xing
Published: August 2022

In time-domain astronomy, a substantial number of transients will be discovered by multi-wavelength and multi-messenger observatories, posing a great challenge for follow-up capabilities. We have thus proposed an intelligent X-ray constellation, the Chasing All Transients Constellation Hunters (CATCH) space mission. Consisting of 133 micro-satellites in four types, CATCH will have the capability to perform follow-up observations for a large number of different types of transients simultaneously. Each satellite in the constellation will carry lightweight X-ray optics and use a deployable mast to increase the focal length. The combination of different optics and detector systems enables different types of satellites to have multiform observation capabilities, including timing, spectroscopy, imaging, and polarization. Controlled by the intelligent system, different satellites can cooperate to perform uninterrupted monitoring, all-sky follow-up observations, and scanning observations with a flexible FOV and multi-dimensional observations. Therefore, CATCH will be a powerful mission to study the dynamic universe. Here, we present the current design of the spacecraft, optics, detector system, constellation configuration and observing modes, as well as the development plan.
Electroactive CTAB/PVDF composite film based Photo-rechargeable Hybrid Power Cell for Clean Energy Generation and Storage
Authors: Molla Sanoar , Khatun Farha , Rajak Ujjwal , Bagchi Biswajoy , Das Sukhen , Thakur Pradip
Published: August 2022

Herein, electroactive polymer based photo-induced hybrid power cell has been developed using CTAB/PVDF composite film in a sustainable manner. First high dielectric polymer film has been prepared by doping CTAB in PVDF matrix via solution casting method. In the basic configuration of this hybrid power cell, aqueous electrolyte solution of PVA-MnO2-Eosin Y has been utilized as solar light absorber and photo-electron generator whereas the high dielectric CTAB/PVDF (~ 400) is used as dielectric separator cum storage part in a very transparent way. The cell shows maximum voltage ~1.1 V with short-circuit current density ~ 7.83 mA/cm2 under ~110 mW /cm2 normal light illumination. The device reveal almost same performance for a long time (30 days). The high storage impact of the hybrid cell is investigated by its promising conversion efficiency ~ 4.48 % with energy density and power density ~26.9 mWhr/m2 and ~5.5 W/m2 respectively.