bluuebunny/crossref_metadata_2025_split huggingface dataset:
Smallest graphs with given generalized quaternion automorphism group
Authors: Graves Christina , Graves Stephen J. , Lauderdale L.‐K. 
Published: June 2017

AbstractFor , a smallest graph whose automorphism group is isomorphic to the generalized quaternion group is constructed. If , then such a graph has vertices and edges. In the special case when , a smallest graph has 16 vertices but 44 edges.
Cantharidin inhibits competitively heme‐Fe(III) binding to the FA1 site of human serum albumin
Authors: Polticelli Fabio , Leboffe Loris , Tortosa Valentina , Trezza Viviana , Fanali Gabriella , Fasano Mauro , Ascenzi Paolo 
Published: June 2017

AbstractCantharidin, a monoterpene isolated from the insect blister beetle, has long been used as a medicinal agent in the traditional Chinese medicine. Cantharidin inhibits a subgroup of serine/threonine phosphatases, thus inducing cell growth inhibition and cytotoxicity. Cantharidin has anticancer activity in vitro, since it is able of inducing p53‐dependent apoptosis and double‐strand breakage of DNA in cancer cells. Although the toxicity of cantharidin to the gastrointestinal and urinary tracts prevents its medical use, it is a promising lead compound for chemical modification to develop new anticancer therapeutics. In fact, cantharidin does not cause myelosuppression and displays anticancer activity against cells with a multidrug resistance phenotype. Here, the competitive inhibitory effect of cantharidin on heme‐Fe(III) binding to the fatty acid site 1 (FA1) of human serum albumin (HSA) is reported. Docking and molecular dynamics simulations support functional data indicating the preferential binding of cantharidin to the FA1 site of HSA. Present results may be relevant in vivo as HSA could transport cantharidin, which in turn could affect heme‐Fe(III) scavenging by HSA.
Computational modeling of the bat HKU4 coronavirus 3CLpro inhibitors as a tool for the development of antivirals against the emerging Middle East respiratory syndrome (MERS) coronavirus
Authors: Abuhammad Areej , Al‐Aqtash Rua'a A. , Anson Brandon J. , Mesecar Andrew D. , Taha Mutasem O. 
Published: June 2017

AbstractThe Middle East respiratory syndrome coronavirus (MERS‐CoV) is an emerging virus that poses a major challenge to clinical management.The 3C‐like protease (3CLpro) is essential for viral replication and thus represents a potential target for antiviral drug development. Presently, very few data are available on MERS‐CoV 3CLpro inhibition by small molecules. We conducted extensive exploration of the pharmacophoric space of a recently identified set of peptidomimetic inhibitors of the bat HKU4‐CoV 3CLpro. HKU4‐CoV 3CLpro shares high sequence identity (81%) with the MERS‐CoV enzyme and thus represents a potential surrogate model for anti‐MERS drug discovery. We used 2 well‐established methods: Quantitative structure‐activity relationship (QSAR)‐guided modeling and docking‐based comparative intermolecular contacts analysis. The established pharmacophore models highlight structural features needed for ligand recognition and revealed important binding‐pocket regions involved in 3CLpro‐ligand interactions. The best models were used as 3D queries to screen the National Cancer Institute database for novel nonpeptidomimetic 3CLpro inhibitors. The identified hits were tested for HKU4‐CoV and MERS‐CoV 3CLpro inhibition. Two hits, which share the phenylsulfonamide fragment, showed moderate inhibitory activity against the MERS‐CoV 3CLpro and represent a potential starting point for the development of novel anti‐MERS agents. To the best of our knowledge, this is the first pharmacophore modeling study supported by in vitro validation on the MERS‐CoV 3CLpro.Highlights

MERS‐CoV is an emerging virus that is closely related to the bat HKU4‐CoV.
3CLpro is a potential drug target for coronavirus infection.
HKU4‐CoV 3CLpro is a useful surrogate model for the identification of MERS‐CoV 3CLpro enzyme inhibitors.
dbCICA is a very robust modeling method for hit identification.
The phenylsulfonamide scaffold represents a potential starting point for MERS coronavirus 3CLpro inhibitors development.
Molecular basis for the recognition of CCN1 by monoclonal antibody 093G9
Authors: Zhong Chen , Huo Rongfen , Hu Kuan , Shen Jinlong , Li Dangsheng , Li Ningli , Ding Jianping 
Published: June 2017

AbstractCCN1, also named Cyr61 (cysteine‐rich protein 61), is the first identified member of the CCN family that is composed of 6 secreted extracellular matrix‐associated glycoproteins. CCN1 has been demonstrated to participate in pathogenesis of rheumatoid arthritis through various pathways. A monoclonal antibody, namely, 093G9, is effective to antagonize the effects of CCN1 and hence has potential therapeutic benefits against rheumatoid arthritis. Here, we show that the epitope recognized by 093G9 is mapped to residues 77 to 80 of CCN1, and a cyclic peptide encompassing residues 75 to 81 of CCN1 displays high binding affinity for 093G9. The crystal structure of the 093G9 Fab in complex with the cyclic peptide was determined at 2.7 Å resolution, which reveals the intensive interactions between CCN1 and 093G9. Particularly, residues Asn79 and Phe80 of CCN1 are inserted into cavities mainly formed by residues of complementarity‐determining region loop L3 and framework region L2 and by residues of complementarity‐determining region loops H2 and H3, respectively, which contribute most of the interactions and therefore are critical for the recognition by 093G9. Together, these findings not only identify the epitope of CCN1 for 093G9 but also reveal the molecular mechanism of recognition and binding of CCN1 by 093G9.
Experimental and computational characterization on the binding of two fluoroquinolones to bovine hemoglobin
Authors: Qin Pengfei , Pan Xingren , Liu Rutao , Qiu Jicai , Fang Xiaoyan 
Published: June 2017

AbstractCiprofloxacin (CPFX) and enrofloxacin (ENFX) are 2 representatives of widely used fluoroquinolones (FQs) with many human and veterinary applications. The residues of FQs in the environment are potentially harmful. Recently, great concern has been paid to their persistence and fate in the environment because of the potential adverse effects on humans and ecosystem functions. In the present study, we examined the interactions of bovine hemoglobin (BHb) with these 2 FQs by means of multiple spectroscopic and molecular docking methods under physiological conditions. The experimental results revealed that both FQs could bind with BHb to form complexes mainly through electrostatic interactions. And CPFX posed more of an affinity threat to BHb than ENFX. On the basis of molecular docking, both FQs could bind into the central cavity of BHb and interact with the residue Trp 37, resulting in the remarkable fluorescence quenching of protein. Additionally, as shown by the synchronous fluorescence, UV‐visible absorption and circular dichroism data, both CPFX and ENFX could lead to the conformational and microenvironmental changes of BHb, which may affect its physiological functions. The work is beneficial for understanding the biological toxicity of FQs in vivo.
Influence of universal HBV vaccination on chronic HBV infection in Italy: Results of a cross‐sectional multicenter study
Authors: Sagnelli Evangelista , Stroffolini Tommaso , Sagnelli Caterina , Morisco Filomena , Coppola Nicola , Smedile Antonina , Pisaturo Mariantonietta , Colloredo Guido , Babudieri Sergio , Licata Anna , Brancaccio Giuseppina , Andriulli Angelo , Almasio Piero L. , Gaeta Giovani B. ,   on behalf of the EPACRON study group
Published: June 2017

Background and AimThe universal hepatitis B vaccination for infants and 12‐year‐old adolescents (the latter limited to the first 12 years of application) was launched in Italy in 1991. Twenty‐three years later we evaluated the impact of the vaccination campaign on the burden of HBsAg‐positive chronic liver diseases (CLD).Material and MethodsA total of 513 HBsAg‐positive chronic carriers referring to 16 Italian liver units were investigated and compared with HBsAg carriers enrolled in previous surveys.ResultsThe proportion of inactive carriers decreased from 20.0% in 2001 to 3.3% in 2014, while that of cirrhotic patients increased from 22.6% to 33.2%. Regarding the age class 0‐33 (fully covered by HBV vaccination in 2014), the rate of inactive carriers decreased from the 21.7% in 2001 to 5.9% in 2014, that of chronic hepatitis from 17.5% to 5.2% and that of cirrhosis cases from 26.4% to 4.1%. Instead, in the over‐60 age group the rate of inactive carriers increased from 22.8% to 41.2% and that of chronic hepatitis from 16.8% to 46%; the rate of patients with cirrhosis ranged from 5% to 8% in different studies.ConclusionTwenty‐three years after the introduction universal HBV vaccination in Italy, the clinical presentation of CLD had shown a shift toward older ages and more severe diseases.
Diffusion MRI and the detection of alterations following traumatic brain injury
Authors: Hutchinson Elizabeth B. , Schwerin Susan C. , Avram Alexandru V. , Juliano Sharon L. , Pierpaoli Carlo 
Published: June 2017

AbstractThis article provides a review of brain tissue alterations that may be detectable using diffusion magnetic resonance imaging MRI (dMRI) approaches and an overview and perspective on the modern dMRI toolkits for characterizing alterations that follow traumatic brain injury (TBI). Noninvasive imaging is a cornerstone of clinical treatment of TBI and has become increasingly used for preclinical and basic research studies. In particular, quantitative MRI methods have the potential to distinguish and evaluate the complex collection of neurobiological responses to TBI arising from pathology, neuroprotection, and recovery. dMRI provides unique information about the physical environment in tissue and can be used to probe physiological, architectural, and microstructural features. Although well‐established approaches such as diffusion tensor imaging are known to be highly sensitive to changes in the tissue environment, more advanced dMRI techniques have been developed that may offer increased specificity or new information for describing abnormalities. These tools are promising, but incompletely understood in the context of TBI. Furthermore, model dependencies and relative limitations may impact the implementation of these approaches and the interpretation of abnormalities in their metrics. The objective of this paper is to present a basic review and comparison across dMRI methods as they pertain to the detection of the most commonly observed tissue and cellular alterations following TBI.
The loss of a fellow service member: Complicated grief in post‐9/11 service members and veterans with combat‐related posttraumatic stress disorder
Authors: Simon Naomi M. , O'Day Emily B. , Hellberg Samantha N. , Hoeppner Susanne S. , Charney Meredith E. , Robinaugh Donald J. , Bui Eric , Goetter Elizabeth M. , Baker Amanda W. , Rogers Andrew H. , Nadal‐Vicens Mireya , Venners Margaret R. , Kim Hyungjin M. , Rauch Sheila A.M. 
Published: June 2017

AbstractBereavement is a potent and highly prevalent stressor among service members and veterans. However, the psychological consequences of bereavement, including complicated grief (CG), have been minimally examined. Loss was assessed in 204 post‐9/11, when service members and veterans with combat‐related posttraumatic stress disorder (PTSD) took part in a multicenter treatment study. Those who reported the loss of an important person completed the inventory of complicated grief (ICG; n = 160). Over three quarters (79.41%) of the sample reported an important lifetime loss, with close to half (47.06%) reporting the loss of a fellow service member (FSM). The prevalence of CG was 24.75% overall, and nearly one third (31.25%) among the bereaved. CG was more prevalent among veterans who lost a fellow service member (FSM) (41.05%, n = 39) compared to those bereaved who did not (16.92%, n = 11; OR = 3.41, 95% CI: 1.59, 7.36). CG was associated with significantly greater PTSD severity, functional impairment, trauma‐related guilt, and lifetime suicide attempts. Complicated grief was prevalent and associated with adverse psychosocial outcomes in veterans and service members with combat‐related PTSD. Clinicians working with this population should inquire about bereavement, including loss of a FSM, and screen for CG. Additional research examining CG in this population is needed.
Resolving the contributions of anaesthesia, surgery, and nerve injury on brain derived neurotrophic factor expression in the medial prefrontal cortex of male rats in the CCI model of neuropathic pain
Authors: Kang James W.M. , Keay Kevin A. , Mor David 
Published: June 2017

AbstractThe medial prefrontal cortex (mPFC) is critical for selecting and shaping complex behavioral responses. In rodent models of neuropathic pain there is evidence for both structural and functional changes in the mPFC. Brain derived neurotrophic factor (BDNF) plays a critical role in the normal functioning of the mPFC. It has been suggested that the disruption of complex behaviors and mood seen in some neuropathic pain patients is mediated in part by alterations of BDNF in this cortical region. In Sprague‐Dawley rats, mPFC levels of BDNF and TrkB mRNA and protein, were quantified and compared to controls (n = 24) 6 days after either: (a) halothane (1.5%) anaesthesia (n = 12), (b) sham surgery under halothane (n = 12), (c) sciatic nerve chronic constriction injury under halothane (n = 48). The social behaviors of the rats were quantified daily during the experimental period. Halothane anaesthesia increased BDNF and TrkB mRNA bilaterally. These increases were reversed in rats that underwent sham surgical and nerve injury procedures. Further, halothane anaesthesia, surgical procedures, and nerve injury each decreased BDNF protein levels. These results reveal a marked and distinct BDNF expression profile in the mPFC of rats that have undergone each stage of the procedure to produce neuropathic pain by chronic constriction injury of the sciatic nerve. The highly sensitive nature of neurotrophic signalling to general anaesthesia in the mature neuronal circuit of the adult rat brain highlights the importance of careful evaluation and interpretation of data evaluating the effects of experimental procedures on neural substrates.
Acute glucose and lactate metabolism are associated with cognitive recovery following traumatic brain injury
Authors: Mannino Christina , Glenn Thomas C. , Hovda David A. , Vespa Paul M. , McArthur David L. , Van Horn John D. , Wright Matthew J. 
Published: June 2017

AbstractTraumatic brain injury (TBI) is associated with acute cerebral metabolic crisis (ACMC). ACMC‐related atrophy appears to be prominent in frontal and temporal lobes following moderate‐to‐severe TBI. This atrophy is correlated with poorer cognitive outcomes in TBI. The current study investigated ability of acute glucose and lactate metabolism to predict long‐term recovery of frontal‐temporal cognitive function in participants with moderate‐to‐severe TBI. Cerebral metabolic rate of glucose and lactate were measured by the Kety‐Schmidt method on days 0–7 post‐injury. Indices of frontal‐temporal cognitive processing were calculated for six months post‐injury; 12 months post‐injury; and recovery (the difference between the six‐ and 12‐month scores). Glucose and lactate metabolism were included in separate regression models, as they were highly intercorrelated. Also, glucose and lactate values were centered and averaged and included in a final regression model. Models for the prediction frontal‐temporal cognition at six and 12 months post‐injury were not significant. However, average glucose and lactate metabolism predicted recovery of frontal‐temporal cognition, accounting for 23% and 22% of the variance, respectively. Also, maximum glucose metabolism, but not maximum lactate metabolism, was an inverse predictor in the recovery of frontal‐temporal cognition, accounting for 23% of the variance. Finally, the average of glucose and lactate metabolism predicted frontal‐temporal cognitive recovery, accounting for 22% of the variance. These data indicate that acute glucose and lactate metabolism both support cognitive recovery from TBI. Also, our data suggest that control of endogenous fuels and/or supplementation with exogenous fuels may have therapeutic potential for cognitive recovery from TBI.
Quantitative profiling of neurotransmitter abnormalities in brain, cerebrospinal fluid, and serum of experimental diabetic encephalopathy male rat
Authors: Han Xiaowen , Min Mengjun , Wang Juan , Bao Zejun , Fan Hongbin , Li Xinyu , Adelusi Temitope Isaac , Zhou Xueyan , Yin Xiaoxing 
Published: June 2017

AbstractDiabetic encephalopathy (DE), one of the most prevalent chronic complications of diabetes mellitus, is short of effective prevention and formidable therapeutic strategies. The aim of the present study is to reveal the imbalance of tryptophan (Trp) and its metabolites in streptozotocin (STZ)‐induced experimental DE rats to underscore their critical values in clinical diagnosis of the disease. For this purpose, we first developed an accurate and appropriate simultaneous method for measuring Trp and its metabolites using liquid chromatography–tandem mass spectrometry, which was in accordance with the requirements of biological sample analysis. Secondly, a single STZ intraperitoneal injection was administered to male Sprague–Dawley rats, and their cognitive function was detected by Morris water maze tests. Cerebrospinal fluid (CSF), serum, and brain tissue were then collected for the determination of Trp and its metabolites. Compared with age‐matched control rats, the levels of neuroprotective serotonin decreased significantly in the samples of cortices, hippocampi, striatum, CSF, and serums in the STZ‐induced DE rats, while the levels of neurotoxic 3‐hydroxykynurenine increased significantly. Moreover, analogous changes of both compounds were found in the central nervous system and peripheral blood of the STZ‐induced DE rats. In conclusion, we established a quantitative method for the simultaneous detection of Trp and its metabolites, and we also present a critical elucidation of the nervous system dysfunction in DE.
Endothelial nitric oxide synthase inhibition triggers inflammatory responses in the brain of male rats exposed to ischemia‐reperfusion injury
Authors: Greco Rosaria , Demartini Chiara , Zanaboni Anna Maria , Blandini Fabio , Amantea Diana , Tassorelli Cristina 
Published: June 2017

AbstractNitric oxide (NO) derived from endothelial NO synthase (eNOS) plays a role in preserving and maintaining the brain's microcirculation, inhibiting platelet aggregation, leukocyte adhesion, and migration. Inhibition of eNOS activity results in exacerbation of neuronal injury after ischemia by triggering diverse cellular mechanisms, including inflammatory responses.To examine the relative contribution of eNOS in stroke‐induced neuroinflammation, we analyzed the effects of systemic treatment with l‐N‐(1‐iminoethyl)ornithine (L‐NIO), a relatively selective eNOS inhibitor, on the expression of MiR‐155‐5p, a key mediator of innate immunity regulation and endothelial dysfunction, in the cortex of male rats subjected to transient middle cerebral artery occlusion (tMCAo) followed by 24 hr of reperfusion. Inducible NO synthase (iNOS) and interleukin‐10 (IL‐10) mRNA expression were evaluated by real‐time polymerase chain reaction in cortical homogenates and in resident and infiltrating immune cells isolated from ischemic cortex. These latter cells were also analyzed for their expression of CD40, a marker of M1 polarization of microglia/macrophages.tMCAo produced a significant elevation of miR155‐5p and iNOS expression in the ischemic cortex as compared with sham surgery. eNOS inhibition by L‐NIO treatment further elevated the cortical expression of these inflammatory mediators, while not affecting IL‐10 mRNA levels. Interestingly, modulation of iNOS occurred in resident and infiltrating immune cells of the ischemic hemisphere. Accordingly, L‐NIO induced a significant increase in the percentage of CD40+ events in CD68+ microglia/macrophages of the ischemic cortex as compared with vehicle‐injected animals.These findings demonstrate that inflammatory responses may underlie the detrimental effects due to pharmacological inhibition of eNOS in cerebral ischemia.
Analysis of variability and trends of precipitation extremes in Singapore during 1980–2013
Authors: Li Xin , Wang Xuan , Babovic Vladan 
Published: June 2017

ABSTRACTChanges in precipitation extremes in the tropical urban context is complex, where the precipitation activities are influenced by the combined effects of El Niño–Southern Oscillation (ENSO), global warming and local effects. This study presents a comprehensive framework to investigate the variability and trends in precipitation extremes in a tropical urban city‐state, Singapore, based on a set of extreme indices recommended by the Expert Team on Climate Change Detection and Indices (ETCCDI). The long‐term trends in the precipitation extremes over the period from 1980 until 2013 are examined using an iterative‐based Mann–Kendall trend test. Besides, the relative importance of precipitation frequency and intensity in inter‐annual variability of wet‐day precipitation totals is investigated. Finally, the correlations between precipitation extremes and three potential large‐scale and local factors, i.e.ENSO, global mean temperature and local temperature are analysed based on linear regression method. Results reveal that annual wet‐day precipitation totals, as well as average wet‐day precipitation intensity, have increased significantly, accompanied by a significant increase in the frequency and intensity of precipitation extremes in Singapore. The inter‐annual variability of wet‐day precipitation totals is mainly dominated by precipitation intensity. Significant correlations are found between precipitation extremes and all the three factors, and the signature of local effects is more evident than global warming. These findings have implications for adaption planning and disaster risk reduction in Singapore in the context of global warming.
Control of abusive water addition to Octopus vulgaris with non‐destructive methods
Authors: Mendes Rogério , Schimmer Ove , Vieira Helena , Pereira João , Teixeira Bárbara 
Published: June 2017

AbstractBACKGROUNDAbusive water addition to octopus has evidenced the need for quick non‐destructive methods for product qualification in the industry and control of fresh commercial products in markets. Electric conductivity (EC)/pH and dielectric property measurements were selected to detect water uptake in octopus.RESULTSA significant EC decrease was determined after soaking octopus in freshwater for 4 h. EC reflected the water uptake of octopus and the correspondent concentration decrease of available ions in the interstitial fluid. Significant correlations were determined between octopus water uptake, EC (R = −0.940) and moisture/protein (M/P) ratio (R = 0.923) changes. Seasonal and spatial variation in proximate composition did not introduce any uncertainty in EC discrimination of freshwater tampering. Immersion in 5 g L−1 sodium tripolyphosphate (STPP) increased EC to a value similar to control octopus. EC false negatives resulting from the use of additives (STPP and citric acid) were eliminated with the additional determination of pH. Octopus soaked in freshwater, STPP and citric acid can also be clearly discriminated from untreated samples (control) and also from frozen (thawed) ones using the dielectric properties. No significant differences in the dielectric property scores were found between octopus sizes or geographical locations.CONCLUSIONSimultaneous EC/pH or dielectric property measurements can be used in a handheld device for non‐destructive water addition detection in octopus. M/P ratio can be used as a reference destructive method. © 2017 Society of Chemical Industry