bluuebunny/crossref_metadata_2025_split huggingface dataset:
DelPhiPKa: Including salt in the calculations and enabling polar residues to titrate
Authors: Pahari Swagata , Sun Lexuan , Basu Sankar , Alexov Emil 
Published: September 2018

AbstractDelPhiPKa is a widely used and unique approach to compute pKa's of ionizable groups that does not require molecular surface to be defined. Instead, it uses smooth Gaussian‐based dielectric function to treat computational space via Poisson‐Boltzmann equation (PBE). Here, we report an expansion of DelPhiPKa functionality to enable inclusion of salt in the modeling protocol. The method considers the salt mobile ions in solvent phase without defining solute‐solvent boundary. Instead, the ions are penalized to enter solute interior via a desolvation penalty term in the Boltzmann factor in the framework of PBE. Hence, the concentration of ions near the protein is balanced by the desolvation penalty and electrostatic interactions. The study reveals that correlation between experimental and calculated pKa's is improved significantly by taking into consideration the presence of salt. Furthermore, it is demonstrated that DelphiPKa reproduces the salt sensitivity of experimentally measured pKa's. Another new development of DelPhiPKa allows for computing the pKa's of polar residues such as cysteine, serine, threonine and tyrosine. With this regard, DelPhiPKa is benchmarked against experimentally measured cysteine and tyrosine pKa's and for cysteine it is shown to outperform other existing methods (DelPhiPKa RMSD of 1.73 vs RMSD between 2.40 and 4.72 obtained by other existing pKaprediction methods).
Real‐time examination of cAMP activity at relaxin family peptide receptors using a BRET‐based biosensor
Authors: Valkovic Adam L. , Leckey Miranda B. , Whitehead Alice R. , Hossain Mohammed A. , Inoue Asuka , Kocan Martina , Bathgate Ross A. D. 
Published: September 2018

AbstractRelaxin family peptide (RXFPs) 1‐4 receptors modulate the activity of cyclic adenosine monophosphate (cAMP) to produce a range of physiological functions. RXFP1 and RXFP2 increase cAMP via Gαs, whereas RXFP3 and RXFP4 inhibit cAMP via Gαi/o. RXFP1 also shows a delayed increase in cAMP downstream of Gαi3. In this study we have assessed whether the bioluminescence resonance energy transfer (BRET)‐based biosensor CAMYEL (cAMP sensor using YFP‐Epac‐Rluc), which allows real‐time measurement of cAMP activity in live cells, will aid in understanding ligand‐ and cell‐specific RXFP signaling. CAMYEL detected concentration‐dependent changes in cAMP activity at RXFP1‐4 in recombinant cell lines, using a variety of ligands with potencies comparable to those seen in conventional cAMP assays. We used RXFP2 and RXFP3 antagonists to demonstrate that CAMYEL detects dynamic changes in cAMP by reversing cAMP activation or inhibition respectively, with real‐time addition of antagonist after agonist stimulation. To demonstrate the utility of CAMYEL to detect cAMP activation in native cells expressing low levels of RXFP receptor, we cloned CAMYEL into a lentiviral vector and transduced THP‐1 cells, which express low levels of RXFP1. THP‐1 CAMYEL cells demonstrated robust cAMP activation in response to relaxin. However, the CAMYEL assay was unable to detect the Gαi3‐mediated phase of RXFP1 cAMP activation in PTX‐treated THP‐1 cells or HEK293A cells with knockout of Gαs. Our data demonstrate that cytoplasmically‐expressed CAMYEL efficiently detects real‐time cAMP activation by Gαs or inhibition by Gαi/o but may not detect cAMP generated in specific intracellular compartments such as that generated by Gαi3 upon RXFP1 activation.
Stevia rebaudianatea prevents experimental cirrhosis via regulation of NF‐κB, Nrf2, transforming growth factor beta, Smad7, and hepatic stellate cell activation
Authors: Ramos‐Tovar Erika , Flores‐Beltrán Rosa E. , Galindo‐Gómez Silvia , Vera‐Aguilar Eunice , Diaz‐Ruiz Araceli , Montes Sergio , Camacho Javier , Tsutsumi Víctor , Muriel Pablo 
Published: September 2018

Stevia has been shown to prevent oxidative stress and inflammation in carbon tetrachloride‐induced cirrhosis models. This study aimed to investigate the ability of an aqueous extract of stevia (AES) to prevent thioacetamide (TAA)‐induced cirrhosis in rats and to explore its mechanism of action. Liver cirrhosis was established by administering TAA (200 mg/kg by i.p. injections three times a week for 10 weeks); AES was administered (100 mg/kg by gavage daily) during the TAA treatment. Liver damage and fibrosis were evaluated, and the profibrotic pathways were analyzed by western blotting and immunohistochemistry. TAA increased nuclear factor kappa B (NF‐κB) and pro‐inflammatory cytokine production, as well as the malondialdehyde and 4‐hydroxynonenal levels, whereas the glutathione/glutathione disulfide and nuclear factor‐E2‐related factor 2 (Nrf2) levels were decreased. Moreover, TAA increased collagen production, hepatic stellate cell (HSC) activation, and expression of profibrogenic mediators. TAA‐treated rats that had been exposed to Mn2+ exhibited altered striatal dopamine turnover, indicating hepatic encephalopathy. AES partially or completely prevented all of these effects. AES showed antioxidant, anti‐inflammatory, and antifibrotic properties, probably because of its capacity to induce Nrf2 expression, reduce NF‐κB expression, and block several profibrogenic signaling pathways, subsequently inhibiting HSC activation and preventing fibrosis and dopamine turnover.
Selective binding of an organoruthenium complex to G‐rich human telomeric sequence by tandem mass spectrometry
Authors: Cheng Yiyu , Zeng Wenjuan , Cheng Yang , Zhang Jishuai , Zou Tao , Wu Kui , Wang Fuyi 
Published: September 2018

RationaleHuman telomeric DNA is reported to be a potential target for anticancer organometallic ruthenium(II) complexes, however, the interaction sites were not clearly discriminated and identified.MethodsIn the current study, tandem mass spectrometry (MS/MS) using collision‐induced dissociation (CID) was firstly introduced to identify the interaction sites of an organometallic ruthenium(II) complex [(η6‐biphenyl)Ru(en)Cl][PF6] (1; en = ethylenediamine) with 5′‐T1T2A3G4G5G6‐3′ (I), the repeating unit of human telomeric DNA, in both positive‐ and negative‐ion mode at a low reaction molar ratio (1/I = 0.2) which was applied to preserve the site selectivity.ResultsMass spectrometric results showed that mono‐ruthenated I was the main product under the conditions. In positive‐ion mode, MS/MS results indicated that ruthenium complex 1 binds to T2 or G6 in strand I. However, in negative‐ion mode, no efficient information was obtained for exact identification of ruthenation sites which may be attributed to losses of fragment ions due to charge neutralization by the coordination of the positively charged ruthenium complex to the short MS/MS fragments.ConclusionsThis is the first report of using top‐down MS to characterize the interactions of organometallic ruthenium(II) complexes and human telomeric DNA. Thymine can be thermodynamically competitive with guanine for binding to ruthenium complexes even at low reaction molar ratio, which inspired us to explore in greater depth the significance of thymine binding.
Emerging trends of Nipah virus: A review
Authors: Sharma Vikrant , Kaushik Sulochana , Kumar Ramesh , Yadav Jaya Parkash , Kaushik Samander 
Published: September 2018

SummarySince emergence of the Nipah virus (NiV) in 1998 from Malaysia, the NiV virus has reappeared on different occasions causing severe infections in human population associated with high rate of mortality. NiV has been placed along with Hendra virus in genus Henipavirus of family Paramyxoviridae. Fruit bats (Genus Pteropus) are known to be natural host and reservoir of NiV. During the outbreaks from Malaysia and Singapore, the roles of pigs as intermediate host were confirmed. The infection transmitted from bats to pigs and subsequently from pigs to humans. Severe encephalitis was reported in NiV infection often associated with neurological disorders. First NiV outbreak in India occurred in Siliguri district of West Bengal in 2001, where direct transmission of the NiV virus from bats‐to‐human and human‐to‐human was reported in contrast to the role of pigs in the Malaysian NiV outbreak. Regular NiV outbreaks have been reported from Bangladesh since 2001 to 2015. The latest outbreak of NiV has been recorded in May, 2018 from Kerala, India which resulted in the death of 17 individuals. Due to lack of vaccines and effective antivirals, Nipah encephalitis poses a great threat to public health. Routine surveillance studies in the infected areas can be useful in detecting early signs of infection and help in containment of these outbreaks.
Frequency of Opercular Deformities in Age‐0 Native Catostomids in the San Juan River from 1998 to 2012
Authors: Barkstedt Judith M. , Clark Barkalow Stephani L. , Farrington Michael A. , Kennedy Jennifer L. , Platania Steven P. 
Published: September 2018

AbstractIn the San Juan River, the recruitment of early ontogenetic stages of federally endangered Razorback Sucker Xyrauchen texanus to subadult or adult stages is rare. Opercular deformities have been detected in larval and early juvenile Razorback Suckers in the San Juan River and were investigated as an impediment to recovery of the species. Larval and early juvenile (age‐0) native San Juan River catostomids taken from 1998 to 2012 were examined for presence of opercular deformities. The frequency and severity of opercular deformities in Razorback Suckers were compared with opercular deformities in Bluehead Sucker Catostomus discobolus and Flannelmouth Sucker Catostomus latipinnis and with hatchery‐produced Razorback Suckers. Deformities were primarily observed in larval stages and occurred both unilaterally and bilaterally. Opercular deformities were relatively consistent among years for all three species. The frequency of opercular deformities in Razorback Suckers was more than three times higher than in Bluehead Suckers and more than five times higher than in Flannelmouth Suckers. Opercular deformities in all species were high when compared with Razorback Sucker brood stock and with wild fish in other river basins. This high rate of deformity in larvae and early juvenile San Juan River Razorback Suckers likely increases mortality and inhibits recruitment to later life stages.
Involvement of P38 and ERK1/2 in mitochondrial pathways independent cell apoptosis in oviduct magnum epithelial cells of layers challenged with vanadium
Authors: Wang Jian‐Ping , Huang Xuan‐Yang , Zhang Ke‐Ying , Ding Xue‐Mei , Zeng Qiu‐Feng , Bai Shi‐Ping , Celi Pietro , Yan Lei , Peng Huan‐Wei , Mao Xiang‐Bing 
Published: September 2018

AbstractVanadium (V) can induce cell apoptosis in layers' oviduct resulting in egg quality reduction. In this study, we investigated the relationship between the mitogen‐activated protein kinase (MAPK)‐signaling pathway and V‐induced apoptosis in poultry oviduct magnum epithelial cells (OMECs). Cultured OMECs were divided into 8 treatment groups: 0 μmol/L V (control), 100 μmol/L V (V100), V100 + P38MAPK inhibitor (SB203580), SB203580, V100 + extracellular signal‐regulated kinases 1 and 2 (ERK1/2) inhibitor (U0126), U0126, V100 + c‐JUN NH2‐terminal kinase (JNK) inhibitor (SP600125), and SP600125. The OMECs were pretreated with the MAPK inhibitors before their treatment with V100 for 12 h. V100 increased the apoptosis of OMECs (P < .05), while 3 MAPK inhibitors suppressed V100‐induced apoptosis P < .05); V100 enhanced the depolarization of △ψm (P < .05), and SB203580 and U0126 alleviated the V100‐induced △ψm decrease (P < .05); V100 downregulated B‐cell lymphoma‐2 (Bcl‐2) and poly [Adenosine diphosphate ribose] polymerase 1 (PARP1) mRNA expression (P < .05), meanwhile it upregulated Bcl‐2 associated x (Bax), Apaf1, cytochrome C (CytC) and cysteine aspartase (caspase) 3, 8, 9 mRNA expression (P < .05). All MAPKs inhibitors alleviated the up‐regulation of V100 for Bax and caspase 3 mRNA expression and down‐regulation of V100 for Bcl‐2 expression (P < .05). SB203580 and U0126 upregulated CytC expression treated by V100 (P < .05), except SP600125, while SB203580 administration resulted in a similar upregulation of PARP1 expression (P < .05). SP600125 can alleviated V triggered p‐P38MAPK (phosphor‐P38), p‐ERK1/2 (phosphor‐ERK1/2), p‐JNK (phosphor‐JNK) increase on OME cells, and SB203580 and U0126 had a similar response to phosphor‐P38 and p‐JNK (P < .05). It concluded that V‐induced apoptosis in OMECs through the activation of P38 and ERK1/2, and by increasing the ratio of Bax/Bcl‐2, which resulted in △ψm decrease, CytC release into the cytosol; consequently caspase 3 is recruited and activated, PARP1 is cleaved, eventually leading to apoptosis.
Propamocarb exposure decreases the secretion of neurotransmitters and causes behavioral impairments in mice
Authors: Zhang Yi , Jin Cuiyuan , Wang Xiaoyu , Shen Manlu , Zhou Jiajie , Wu Sisheng , Fu Zhengwei , Jin Yuanxiang 
Published: September 2018

AbstractPropamocarb (PM) is a type of fungicide, which is widely used in the greenhouse‐based production of vegetables and fruits globally. It has been considered to have generally low toxicity. However, the teratogenicity or neurotoxicity for mammals remains unclear. In this study, we aimed to explore its effect on the secretion of neurotransmitters and behavioral impairments. Male adult mice were exposed to 10 and 40 mg/L PM for 2 weeks (acute exposure) or 3 and 10 mg/L PM for 10 weeks (chronic exposure). It was observed that acute or chronic exposure to PM changed the levels of serotonin (5‐HT) and dopamine in the serum and colon and the transcription of TPH2 and DRD2 in the colons of mice. In addition, the locomotor test, the open field test, and the Morris water maze analysis also showed that acute exposure to PM caused behavioral impairments to some extent. The results obtained in the present study indicated that PM has the potential to induce neurotoxicity in animals.
Dynamic and reversible RNA N6‐methyladenosine methylation
Authors: Duan Hong‐Chao , Wang Ye , Jia Guifang 
Published: September 2018

N6‐methyladenosine (m6A) is the most abundant internal chemical modification in eukaryotic messenger RNAs (mRNAs). The discovery in 2011 that m6A is reversed by the fat mass and obesity‐associated protein stimulated extensive worldwide research efforts on the regulatory biological functions of dynamic m6A and other RNA modifications. The epitranscriptomic mark m6A is written, read, and erased through the activities of a complicated network of enzymes and other proteins. m6A‐binding proteins read m6A marks and transduce their downstream regulatory effects by altering RNA metabolic processes. In this review, we summarize the current knowledge of m6A modifications, with particular focus on the functions of its writer, eraser, and reader proteins in posttranscriptional gene regulation and discuss the impact of m6A marks on human health.This article is categorized under:

RNA Processing > RNA Editing and Modification
RNA in Disease and Development > RNA in Disease
Three‐dimensional vibration analysis of simply supported laminated cylindrical shells and panels by a strong SaS formulation
Authors: Kulikov G. M. , Plotnikova S. V. , Kulikov M. G. 
Published: September 2018

AbstractIn this paper, the strong sampling surfaces (SaS) formulation developed earlier by the authors to solve the statics problems for plates and shells is extended to the three‐dimensional (3D) vibration analysis of laminated composite shells. The SaS formulation is based on choosing the arbitrary number of SaS parallel to the middle surface in order to introduce the displacements of these surfaces as basic shell unknowns. Such choice of unknowns with the use of Lagrange polynomials in approximations of displacements and strains through the layer thicknesses leads to a robust laminated shell formulation. The feature of the proposed strong SaS formulation is that all SaS are located inside the layers at Chebyshev polynomial nodes. The use of outer surfaces and interfaces is avoided that makes possible to minimize uniformly the error due to Lagrange interpolation. Therefore, the strong SaS formulation based on direct integration of equations of motion of the elastic body can be applied efficiently for the 3D vibration analysis of laminated cylindrical shells and panels.
Introduction: The Study and Reception of Aristotle’s Parva naturalia
Authors: Bydén Börje 
Published: September 2018

Abstract
The thirteen essays that make up the bulk of this volume all began as papers or comments on papers presented at the first Representation and Reality conference in Gothenburg on 6–8 June 2014 (“Cross-Cultural Dialogues: The Parva naturalia in Greek, Arabic and Latin Aristotelianism”). They are perhaps most straightforwardly read as accounts of so many episodes in the history of the ancient and medieval reception of a classical philosophical work, Aristotle’s Parva naturalia. By and large, they can also be read as inquiries into different passages in the development of a specific theme (psycho-physiology, for want of a better term) in the history of ancient and medieval philosophy. For in ancient and medieval times, the reception of classical philosophical works, not least Aristotle’s, was part of the daily business of philosophers, not historians. Each of these accounts (or inquiries) presents original research designed to widen and deepen our understanding of the episode in hand.
Mothers, Media, and Individualism in Public Policy
Authors: Crane Jennifer 
Published: September 2018

Abstract‘Mothers, Media, and Individualism’ focuses on the role of television and newspapers in constructing concerns about child protection in the late twentieth century, particularly through focus on the experiences and emotions of mothers. The chapter demonstrates that media interest in mothers has often portrayed women as hysterical, and has focused particularly on women’s campaigning against paedophilia. Nonetheless, the chapter also traces cases in which women themselves exerted control over media representations, harnessing journalistic interest to direct attention to their own agendas or cases. Looking to the late 1990s, and to the New Labour moment, the chapter further demonstrates that parental campaigning has become more embedded in public policy over the late twentieth century, shifting from disorganised protest to calculated collective action, whereby mothers held influential individual positions in Tony Blair’s ‘sofa government’.
The Visibility of Survivors and Experience as Expertise
Authors: Crane Jennifer 
Published: September 2018

Abstract
This chapter explores a variety of spaces in which people who had been abused in childhood—survivors—began to speak publicly about their experiences from the 1970s, 1980s, and in particular from the 1990s. It analyses survivor testimony in agony aunt columns, memoirs, academic study, and through newly formed campaign groups. In doing so, the chapter assesses why and how public policy interest in survivors developed decades after focus on children and parents, alongside broader interest in tracing trauma through the life course. Survivor representatives developed significant positions of influence in public policy and media in the last decade of the twentieth century, though nonetheless voluntary groups also struggled to gain government funding, and often felt that their inclusion in political processes was tokenistic. This chapter again traces a growing public policy focus on individual community representatives in the New Labour years, and it demonstrates how voluntary leaders drew on professional, experiential, and emotional expertise.
Hydrodynamics of topological Dirac semi-metals with chiral and ℤ2 anomalies
Authors: Rogatko Marek , Wysokinski Karol I. 
Published: September 2018

AbstractWe consider the hydrodynamical model of topological Dirac semi-metal possessing two Dirac nodes separated in momentum space along a rotation axis. It has been argued that the system in question, except the chiral anomaly, is endowed with the other one ℤ2. In order to model such a system we introduce two U(1)-gauge fields. The presence of the additional ℤ2anomaly leads to the non-trivial modifications of hydrodynamical equations and to the appearance of new kinetic coefficients bounded with the vorticity and the magnetic parts of Maxwell and auxiliary U(1)-gauge fields.
Relationship between physical activity, cognition, and Alzheimer pathology in autosomal dominant Alzheimer's disease
Authors: Müller Stephan , Preische Oliver , Sohrabi Hamid R. , Gräber Susanne , Jucker Mathias , Ringman John M. , Martins Ralph N. , McDade Eric , Schofield Peter R. , Ghetti Bernardino , Rossor Martin , Fox Nick N. , Graff‐Radford Neill R. , Levin Johannes , Danek Adrian , Vöglein Jonathan , Salloway Stephen , Xiong Chengjie , Benzinger Tammie , Buckles Virginia , Masters Colin L. , Sperling Reisa , Bateman Randall J. , Morris John C. , Laske Christoph ,   Dominantly Inherited Alzheimer Network (DIAN)
Published: September 2018

AbstractIntroductionLittle is known about effects of physical activity (PA) in genetically driven early‐onset autosomal dominant Alzheimer's disease (AD).MethodsA total of 372 individuals participating at the Dominantly Inherited Alzheimer Network study were examined to evaluate the cross‐sectional relationship of PA with cognitive performance, functional status, cognitive decline, and AD biomarkers in cerebrospinal fluid. Mutation carriers were categorized as high or low exercisers according to WHO recommendations.ResultsMutation carriers with high PA showed significantly better cognitive and functional performance and significantly less AD‐like pathology in cerebrospinal fluid than individuals with low PA. Mutation carriers with high PA scored 3.4 points better on Mini Mental State Examination at expected symptom onset and fulfilled the diagnosis of very mild dementia 15.1 years later compared with low exercisers.DiscussionThese results support a beneficial effect of PA on cognition and AD pathology even in individuals with genetically driven autosomal dominant AD.
Validation of Portuguese version of the low anterior resection syndrome score
Authors: Rama Nuno José , Ferreira Pedro Lopes , Pimentel João , Juul Therese ,   on behalf of the Portuguese PT LARS Collaborative Group
Published: September 2018

Abstract
Objective The authors aim to perform a thorough translation with cultural adaptation of the patient reported outcome tool, Low Anterior Resection Syndrome (LARS) Score, to the Portuguese language (LARS-PT) in the Portuguese population with rectal cancer, after proctectomy with anastomosis.
Methods According to the current international recommendations, we designed this study encompassing three main phases: (i) cultural and linguistic validation to European Portuguese; (ii) feasibility and reliability tests of the version obtained in the previous phase; and (iii) validity tests to produce a final version. The questionnaire was completed by 154 patients from six Portuguese Colorectal Cancer Units, and 58 completed it twice.
Results Portuguese version of LARS score showed high construct validity. Regarding the test-retest, the global Intraclass Correlation showed very strong test-retest reliability. Looking at all five items, only items 3 and 5 present a moderate correlation. LARS score was able to discriminate symptoms showing worse quality of life, in patients submitted to preoperative radio and chemotherapy.
Conclusions LARS questionnaire has been properly translated into European Portuguese, demonstrating high construct validity and reliability. This is a precise, reproducible, simple, clear and user-friendly tool for evaluating bowel function in rectal cancer patients after sphincter saving operation.