bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biomolecular Interaction, Anti-Cancer and Anti-Angiogenic Properties of Cobalt(III) Schiff Base Complexes
Authors: Ambika Subramanian , Manojkumar Yesaiyan , Arunachalam Sankaralingam , Gowdhami Balakrishnan , Meenakshi Sundaram Kishore Kumar , Solomon Rajadurai Vijay , Venuvanalingam Ponnambalam , Akbarsha Mohammad Abdulkader , Sundararaman Muthuraman 
Published: February 2019

AbstractTwo cobalt(III) Schiff base complexes, trans-[Co(salen)(DA)2](ClO4) (1) and trans-[Co(salophen)(DA)2](ClO4) (2) (where salen: N,N’-bis(salicylidene)ethylenediamine, salopen: N,N’-bis(salicylidene)-1,2-phenylenediamine, DA: dodecylamine) were synthesised and characterised using various spectroscopic and analytical techniques. The binding affinity of both the complexes with CT-DNA was explored adopting UV-visible, fluorescence, circular dichroism spectroscopy and cyclic voltammetry techniques. The results revealed that both the complexes interacted with DNA via intercalation as well as notable groove binding. Protein (BSA) binding ability of these complexes was investigated by absorption and emission spectroscopy which indicate that these complexes engage in strong hydrophobic interaction with BSA. The mode of interaction between these complexes and CT-DNA/BSA was studied by molecular docking analysis. The in vitro cytotoxic property of the complexes was evaluated in A549 (human small cell lung carcinoma) and VERO (African green monkey kidney cells). The results revealed that the complexes affect viability of the cells. AO and EB staining and cell cycle analysis revealed that the mode of cell death is apoptosis. Both the complexes showed profound inhibition of angiogenesis as revealed in in-vivo chicken chorioallantoic membrane (CAM) assay. Of the two complexes, the complex 2 proved to be much more efficient in affecting the viability of lung cancer cells than complex 1. These results indicate that the cobalt(III) Schiff base complexes in this study can be potentially used for cancer chemotherapy and as inhibitor of angiogenesis, in general, and lung cancer in particular, for which there is need for substantiation at the level of signalling mechanisms and gene expressions.
High T2-weighted signal intensity is associated with myocardial deformation in hypertrophic cardiomyopathy
Authors: Shi Ruo-yang , An Dong-aolei , Chen Bing-hua , Wu Rui , Wu Chong-wen , Du Liang , Zhu Jiong , Jiang Meng , Xu Jian-rong , Wu Lian-ming 
Published: February 2019

AbstractThe association between global and segmental myocardial strain impairment and fibrosis extent in hypertrophic cardiomyopathy (HCM) is widely verified. The aim of this study was to investigate the contribution of high T2-weighted signal intensity (HighT2) to myocardial deformation in HCM. We prospectively recruited 57 patients with HCM examined by a 3.0 Tesla magnetic resonance scanner with cine, T2-weighted imaging with fat saturation and phase-sensitive inversion recovery. Global and segmental radial, circumferential and longitudinal strains were included for analysis. The extent of HighT2 was negatively correlated with global radial strain (ρ = −0.275, p = 0.038) and positively correlated with global circumferential strain (ρ = 0.308, p = 0.02) and global longitudinal strain (ρ = 0.422, p = 0.001). Radial, circumferential and longitudinal strains were all significantly associated with segment thickness. Regarding circumferential strain, segments at the mid-ventricular level with LGE and HighT2 showed more impairment than segments with only LGE. For longitudinal strain, the influence of HighT2 appeared only at the mid-ventricular level. The HighT2 extent in HCM was observed to contribute to global and segmental strain parameters. At the segmental level, HighT2 indeed affects left ventricular deformation, and follow-up studies are still warranted.
Substituting the catalytic proline of 4-oxalocrotonate tautomerase with non-canonical analogues reveals a finely tuned catalytic system
Authors: Lukesch Michael S. , Pavkov-Keller Tea , Gruber Karl , Zangger Klaus , Wiltschi Birgit 
Published: February 2019

AbstractThe enzyme 4-oxalocrotonate tautomerase shows remarkable catalytic versatility due to the secondary amine of its N-terminal proline moiety. In this work, we incorporated a range of proline analogues into the enzyme and examined the effects on structure and activity. While the structure of the enzyme remained unperturbed, its promiscuous Michael-type activity was severely affected. This finding demonstrates how atomic changes in a biocatalytic system can abolish its activity. Our work provides a toolbox for successful generation of enzyme variants with non-canonical catalytic proline analogues.
A hindbrain inhibitory microcircuit mediates vagally-coordinated glucose regulation
Authors: Boychuk Carie R. , Smith Katalin Cs. , Peterson Laura E. , Boychuk Jeffery A. , Butler Corwin R. , Derera Isabel D. , McCarthy John J. , Smith Bret N. 
Published: February 2019

AbstractNeurons in the brainstem dorsal vagal complex integrate neural and humoral signals to coordinate autonomic output to viscera that regulate a variety of physiological functions, but how this circuitry regulates metabolism is murky. We tested the hypothesis that premotor, GABAergic neurons in the nucleus tractus solitarius (NTS) form a hindbrain micro-circuit with preganglionic parasympathetic motorneurons of the dorsal motor nucleus of the vagus (DMV) that is capable of modulating systemic blood glucose concentration. In vitro, neuronal activation or inhibition using either excitatory or inhibitory designer receptor exclusively activated by designer drugs (DREADDs) constructs expressed in GABAergic NTS neurons increased or decreased, respectively, action potential firing of GABAergic NTS neurons and downstream synaptic inhibition of the DMV. In vivo, DREADD-mediated activation of GABAergic NTS neurons increased systemic blood glucose concentration, whereas DREADD-mediated silencing of these neurons was without effect. The DREADD-induced hyperglycemia was abolished by blocking peripheral muscarinic receptors, consistent with the hypothesis that altered parasympathetic drive mediated the response. This effect was paralleled by elevated serum glucagon and hepatic phosphoenolpyruvate carboxykinase 1 (PEPCK1) expression, without affecting insulin levels or muscle metabolism. Activity in a hindbrain inhibitory microcircuit is sufficient to modulate systemic glucose concentration, independent of insulin secretion or utilization.
Modelling Holocene analogues of coastal plain estuaries reveals the magnitude of sea-level threat
Authors: Helfensdorfer Anna M. , Power Hannah E. , Hubble Thomas C. T. 
Published: February 2019

AbstractHydrodynamic modelling of Australia’s lower Murray River demonstrates the response of a large coastal plain estuary to the mid-Holocene (7,000–6,000 yr BP) sea-level highstand. The approximately two metre higher-than-present sea level during the highstand forced the estuarine limit upstream generating an extensive central basin environment extending more than 200 kilometres from the river mouth (143 kilometres upstream of the modern tidal limit). The geomorphic history of the region does not conform to conventional estuarine facies models as, for much of the Holocene, the lower Murray River acted as a landward, gorge-confined extension of the Murray estuary. The incredibly low relief of this coastal plain system drove significant saline incursion and limited current velocities across the estuary facilitating deposition of a laminated silt-clay sequence which our results suggest may be regionally extensive. Variations to discharge, barrier morphology, or the estuary’s bathymetry result in minimal change to the estuarine palaeo-environment. The shift to the present-day fresher water distribution in the Murray estuary requires a fall in sea level to present-day conditions. The dominance of sea level as the controlling factor on this estuarine palaeo-environment highlights the significant potential impact of climate change induced sea-level rise to coastal plain estuaries.
Associations of maternal, perinatal and postnatal factors with the eruption timing of the first primary tooth
Authors: Wu Huaying , Chen Ting , Ma Qian , Xu Xiangqin , Xie Kaipeng , Chen Yaming 
Published: February 2019

AbstractWe recruited 1296 mothers in their first trimester from the Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University between May 2014 and September 2015 to investigate the associations of maternal, perinatal and postnatal factors with the eruption timing of the first primary tooth (ETFPT) in a Chinese population. We collected maternal demographic information and clinical data during the perinatal and postnatal period, and oral examinations of the infants were performed by a doctor at 6, 9 and 12 months of age. Multiple regression analysis was used to identify significant explanatory variables for ETFPT. The mean age at eruption of the first primary tooth for all the infants was 6.82 ± 1.90 months. After adjustment for confounders, higher maternal childbearing age (β = 0.57; 95%CI = 0.13–1.02), female sex (β = 0.26; 95%CI = 0.07–0.52), and low birth weight (β = 0.98; 95%CI = 0.20–1.76) were significantly associated with delayed eruption of the first primary tooth, while macrosomia (β = −0.79; 95%CI = −1.30–−0.28) was significantly associated with earlier eruption of the first primary tooth. Maternal childbearing age, infant sex and infant birth weight were significant determinants of ETFPT.
Vascular RAGE transports oxytocin into the brain to elicit its maternal bonding behaviour in mice
Authors: Yamamoto Yasuhiko , Liang Mingkun , Munesue Seiichi , Deguchi Kisaburo , Harashima Ai , Furuhara Kazumi , Yuhi Teruko , Zhong Jing , Akther Shirin , Goto Hisanori , Eguchi Yuya , Kitao Yasuko , Hori Osamu , Shiraishi Yoshitake , Ozaki Noriyuki , Shimizu Yu , Kamide Tomoya , Yoshikawa Akifumi , Hayashi Yasuhiko , Nakada Mitsutoshi , Lopatina Olga , Gerasimenko Maria , Komleva Yulia , Malinovskaya Natalia , Salmina Alla B. , Asano Masahide , Nishimori Katsuhiko , Shoelson Steven E. , Yamamoto Hiroshi , Higashida Haruhiro 
Published: February 2019

AbstractOxytocin sets the stage for childbirth by initiating uterine contractions, lactation and maternal bonding behaviours. Mice lacking secreted oxcytocin (Oxt−/−, Cd38−/−) or its receptor (Oxtr−/−) fail to nurture. Normal maternal behaviour is restored by peripheral oxcytocin replacement in Oxt−/− and Cd38−/−, but not Oxtr−/− mice, implying that circulating oxcytocin crosses the blood-brain barrier. Exogenous oxcytocin also has behavioural effects in humans. However, circulating polypeptides are typically excluded from the brain. We show that oxcytocin is transported into the brain by receptor for advanced glycation end-products (RAGE) on brain capillary endothelial cells. The increases in oxcytocin in the brain which follow exogenous administration are lost in Ager−/− male mice lacking RAGE, and behaviours characteristic to abnormalities in oxcytocin signalling are recapitulated in Ager−/− mice, including deficits in maternal bonding and hyperactivity. Our findings show that RAGE-mediated transport is critical to the behavioural actions of oxcytocin associated with parenting and social bonding.
Key aspects of the iodine metabolism in brown algae: a brief critical review
Authors: Küpper Frithjof C , Carrano Carl J 
Published: February 2019

AbstractBrown algae include the strongest accumulators of iodine known among living systems. This paper reviews the current state of bioinorganic research in the field, focusing on the models Laminaria digitata, Macrocystis pyrifera and Ectocarpus siliculosus, and covering uptake and efflux, localization and biological significance of storage, as well as marine and atmospheric chemistry of iodine.
Catalytic properties of the metal ion variants of mandelate racemase reveal alterations in the apparent electrophilicity of the metal cofactor
Authors: Harty Matthew L , Sharma Amar Nath , Bearne Stephen L 
Published: February 2019

Abstract
Mandalate racemase (MR) from Pseudomonas putida requires a divalent metal cation, usually Mg2+, to catalyse the interconversion of the enantiomers of mandelate. Although the active site Mg2+ may be replaced by Mn2+, Co2+, or Ni2+, substitution by these metal ions does not markedly (&lt;10-fold) alter the kinetic parameters Kmapp, Kcatapp, and (kcat/Km)app for the substrates (R)- and (S)-mandelate, and the alternative substrate (S)-trifluorolactate. Viscosity variation experiments with Mn2+-MR showed that the metal ion plays a role in the uniform binding of the transition states for enzyme–substrate association, the chemical step, and enzyme-product dissociation. Surprisingly, the competitive inhibition constants (Ki) for inhibition of each metalloenzyme variant by benzohydroxamate did not vary significantly with the identity of the metal ion unlike the marked variation of the stability constants (K1) observed for M2+·BzH complex formation in solution. A similar trend was observed for the inhibition of the metalloenzyme variants by F−, except for Mg2+-MR, which bound F− tighter than would be predicted based on the stability constants for formation of M2+·F− complexes in solution. Thus, the enzyme modifies the enatic state of the bound metal ion cofactor so that the apparent electrophilicity of Mg2+ is enhanced, while that of Ni2+ is attenuated, resulting in a levelling effect relative to the trends observed for the free metals in solution.
ParA proteins of secondary genome elements cross-talk and regulate radioresistance through genome copy number reduction in Deinococcus radiodurans
Authors: Kumar Maurya Ganesh , Kota Swathi , Kumar N. Naveen , Tewari Raghvendra , Misra Hari S. 
Published: February 2019

Abstract
Deinococcus radiodurans, an extremely radioresistant bacterium has a multipartite genome system and ploidy. Mechanisms underlying such types of bacterial genome maintenance and its role in extraordinary radioresistance are not known in this bacterium. Chromosome I (Chr I), chromosome II (Chr II) and megaplasmid (Mp) encode its own set of genome partitioning proteins. Here, we have characterized P-loop ATPases of Chr II (ParA2) and Mp (ParA3) and their roles in the maintenance of genome copies and extraordinary radioresistance. Purified ParA2 and ParA3 showed nearly similar polymerization kinetics and interaction patterns with DNA. Electron microscopic examination of purified proteins incubated with DNA showed polymerization on nicked circular dsDNA. ParA2 and ParA3 showed both homotypic and heterotypic interactions to each other, but not with ParA1 (ParA of Chr I). Similarly, ParA2 and ParA3 interacted with ParB2 and ParB3 but not with ParB1 in vivo. ParB2 and ParB3 interaction with cis-elements located upstream to the corresponding parAB operon was found to be sequence-specific. Unlike single mutant of parA2 and parA3, their double mutant (ΔparA2ΔParA3) affected copy number of cognate genome elements and resistance to γ-radiation as well as hydrogen peroxide in this bacterium. These results suggested that ParA2 and ParA3 are DNA-binding ATPases producing higher order polymers on DNA and are functionally redundant in the maintenance of secondary genome elements in D. radiodurans. The findings also suggest the involvement of secondary genome elements such as Chr II and Mp in the extraordinary radioresistance of D. radiodurans.
miR-206 inhibits osteogenic differentiation of bone marrow mesenchymal stem cells by targetting glutaminase
Authors: Chen Ying , Yang Yu-Run , Fan Xiao-Liang , Lin Peng , Yang Huan , Chen Xing-Zuo , Xu Xiao-Dong 
Published: February 2019

AbstractOsteoblast-mediated bone formation is a complex process involving various pathways and regulatory factors, including cytokines, growth factors, and hormones. Investigating the regulatory mechanisms behind osteoblast differentiation is important for bone regeneration therapy. miRNAs are known as important regulators, not only in a variety of cellular processes, but also in the pathogenesis of bone diseases. In the present study, we investigated the potential roles of miR-206 during osteoblast differentiation. We report that miR-206 expression was significantly down-regulated in human bone marrow mesenchymal stem cells (BMSCs) at days 7 and 14 during osteogenic induction. Furthermore, miR-206 overexpressing BMSCs showed attenuated alkaline phosphatase (ALP) activity, Alizarin Red staining, and osteocalcin secretion. The mRNA levels of osteogenic markers, Runx2 and Osteopontin (OPN), were significantly down-regulated in miR-206 overexpressing BMSCs. We observed that significantly increased glutamine uptake at days 7 and 14 during the osteogenic induction and inhibition of glutamine metabolism by knocking down glutaminase (GLS)-suppressed osteogenic differentiation of BMSCs. Here, we discover that miR-206 could directly bind to the 3′-UTR region of GLS mRNA, resulting in suppressed GLS expression and glutamine metabolism. Finally, restoration of GLS in miR-206 overexpressing BMSCs led to recovery of glutamine metabolism and osteogenic differentiation. In summary, these results reveal a new insight into the mechanisms of the miR-206-mediated osteogenesis through regulating glutamine metabolism. Our study may contribute to the development of therapeutic agents against bone diseases.
Microstructure changes in whiter matter relate to cognitive impairment in Wilson’s disease
Authors: Dong Ting , Yang Wen-ming , Wu Ming-cai , Zhang Juan , Huang Peng , Xu Chun-sheng , Wang An-qin , Kuang Chun-jun , Gao Zhi-ling 
Published: February 2019

Abstract
Purpose: Wilson’s disease (WD) is a genetic disorder of copper metabolism with pathological copper accumulation in the brain. The purpose of the present study was to evaluate the relationship between the damaged white matter and the impaired cognitive function in WD patients. Materials and methods: Thirty WD adolescents and thirty age- and sex-matched healthy controls (HC) were enrolled. All subjects had received brain MRI, including conventional and diffusion-tensor imaging (DTI) scans. The DTI parameter of fractional anisotropy (FA) was calculated by diffusion kurtosis estimator software. The t test was used to compare the differences between two groups. The correlation between cognitive function and whiter matter disorders were analyzed by linear regression. The results of FA parameter and MD parameter intergroup analysis were both corrected with False Discovery Rate (FDR) simulations by SPSS. Results: WD adolescents showed significantly lower scores of time-based prospective memory (TBPM) and verbal fluency test (VFT) compared with HC. We found significantly higher FA in the right thalamus, right lentiform nucleus, left thalamus, left lentiform nucleus, and brain stem in WD adolescents. Besides, WD adolescents exhibited significantly lower FA in right cerebellum and cingulum and left middle frontal lobe compared with controls (P&lt;0.05). There were significantly negative correlations between FA in bilateral lentiform and thalamus and cognitive impairment in WD adolescents (P&lt;0.05). Conclusion: The whiter matter of WD adolescents was impaired and mainly distributed in subcortical brain regions. The impaired cognitive function was affected by the damaged whiter matter. The present study may be helpful for recognition and understanding of WD.
Fructose 1,6-bisphosphatase: getting the message across
Authors: Timson David J. 
Published: February 2019

Abstract
Fructose 1,6-bisphosphatase (FBPase) is a key enzyme in gluconeogenesis. It is a potential drug target in the treatment of type II diabetes. The protein is also associated with a rare inherited metabolic disease and some cancer cells lack FBPase activity which promotes glycolysis facilitating the Warburg effect. Thus, there is interest in both inhibiting the enzyme (for diabetes treatment) and restoring its activity (in relevant cancers). The mammalian enzyme is tetrameric, competitively inhibited by Fructose 2,6-bisphosphate and negatively allosterically regulated by AMP. This allosteric regulation requires information transmission between the AMP binding site and the active site of the enzyme. A recent paper by Topaz et al. (Bioscience Reports (2019) 39, pii:BSR20180960) has added additional detail to our understanding of this information transmission process. Two residues in the AMP binding site (Lys112 and Tyr113) were shown to be involved in initiating the message between the two sites. This tyrosine residue has recently be shown to be important with protein’s interaction with the antidiabetic drug metformin. A variant designed to increase metal ion affinity (M248D) resulted in a five-fold increase in enzymatic activity. Interestingly alterations of two residues at the subunit interfaces (Tyr164 and Met177) resulted in increased responsiveness to AMP. Overall, these findings may have implications in the design of novel FBPase inhibitors or activators.
Histone acetylation and DNA methylation in ischemia/reperfusion injury
Authors: Tang Jinhua , Zhuang Shougang 
Published: February 2019

Abstract
Ischemic/reperfusion (I/R) injury causes a series of serious clinical problems associated with high morbidity and mortality in various disorders, such as acute kidney injury (AKI), myocardial infarction, ischemic stroke, circulatory arrest, and peripheral vascular disease. The pathophysiology and pathogenesis of I/R injury is complex and multifactorial. Recent studies have revealed that epigenetic regulation is critically involved in the pathogenesis of I/R-induced tissue injury. In this review, we will sum up recent advances on the modification, regulation, and implication of histone modifications and DNA methylation in I/R injury-induced organ dysfunction. Understandings of I/R-induced epigenetic alterations and regulations will aid in the development of potential therapeutics.
Macrophage migration inhibitory factor plays an essential role in ischemic preconditioning-mediated cardioprotection
Authors: Ruze Amanguli , Chen Bang-Dang , Liu Fen , Chen Xiao-Cui , Gai Min-Tao , Li Xiao-Mei , Ma Yi-Tong , Du Xiao-Jun , Yang Yi-Ning , Gao Xiao-Ming 
Published: February 2019

Abstract
Ischemic preconditioning (IPC) is an endogenous protection strategy against myocardial ischemia–reperfusion (I/R) injury. Macrophage migration inhibitory factor (MIF) released from the myocardium subjected to brief periods of ischemia confers cardioprotection. We hypothesized that MIF plays an essential role in IPC-induced cardioprotection. I/R was induced either ex vivo or in vivo in male wild-type (WT) and MIF knockout (MIFKO) mice with or without proceeding IPC (three cycles of 5-min ischemia and 5-min reperfusion). Indices of myocardial injury, regional inflammation and cardiac function were determined to evaluate the extent of I/R injury. Activations of the reperfusion injury salvage kinase (RISK) pathway, AMP-activated protein kinase (AMPK) and their downstream components were investigated to explore the underlying mechanisms. IPC conferred prominent protection in WT hearts evidenced by reduced infarct size (by 33–35%), myocyte apoptosis and enzymatic markers of tissue injury, ROS production, inflammatory cell infiltration and MCP1/CCR2 expression (all P&lt;0.05). IPC also ameliorated cardiac dysfunction both ex vivo and in vivo. These protective effects were abolished in MIFKO hearts. Notably, IPC mediated further activations of RISK pathway, AMPK and the membrane translocation of GLUT4 in WT hearts. Deletion of MIF blunted these changes in response to IPC, which is the likely basis for the absence of protective effects of IPC against I/R injury. In conclusion, MIF plays a critical role in IPC-mediated cardioprotection under ischemic stress by activating RISK signaling pathway and AMPK. These results provide an insight for developing a novel therapeutic strategy that target MIF to protect ischemic hearts.