bluuebunny/crossref_metadata_2025_split huggingface dataset:
Standard operating procedures (SOP) in experimental stroke research: SOP for middle cerebral artery occlusion in the mouse
Authors: Dirnagl Ulrich ,   Members of the MCAO-SOP Group
Published: July 2019

AbstractRecently, systematic reviews have found quantitative evidence that low study quality may have introduced a bias into preclinical stroke research. Monitoring, auditing, and standard operating procedures (SOPs) are already key elements of quality control in randomized clinical trials and will hopefully be widely adopted by preclinical stroke research in the near future. Increasingly, funding bodies and review boards overseeing animal experiments are taking a proactive stance, and demand auditable quality control measures in preclinical research. Every good quality control system is based on its SOPs. This article introduces the concept of quality control and presents for the first time an SOP in experimental stroke research.
A Study of the Mechanism of Action of Zervamicin IIB Peptide Antibiotic by Molecular Dynamics Simulation
Authors: Shaitan Konstantin , Levtsova Olga , Makarov Vladimir , Kirpichnikov Mikhail 
Published: July 2019

AbstractWe model mechanism of action of a channel-forming peptide antibiotic, zervamicin IIB, by molecular dynamics (MD) simulation. Interaction of this peptide with neutral and negatively charged lipid bilayers is investigated. It is found that charge of membrane surface influences the orientation of zervamicin IIB molecule, that may in turn effect its permeation into the membrane. On this basis we propose modifications to ZrvIIB structure that may increase its affinity towards the prokaryotic cellular membrane. Zervamicin IIB transmembrane channels are modeled as bundles consisting of 4, 5 and 6 individual peptide monomers. Our results suggest that four monomers don’t form a stable water-filled ion channel. Thus the channel with the least number of monomers (and the lowest conductance level by literature data) is a pentamer.
Successive Induction in Larval Zebrafish
Authors: Staddon John , Macphail Robert , Padilla Stephanie 
Published: July 2019

AbstractActivating one reflex often facilitates another, antagonistic one. Since Charles Sherrington first identified successive induction more than 100 years ago, it has been demonstrated in a wide range of species, from aphids to grasshoppers to dogs and humans. We show a particularly orderly example in zebrafish (Danio rerio) larvae and identify the simple dynamic process that seems to underlie it.
Role of chondroitin sulfate proteoglycans (CSPGs) in synaptic plasticity and neurotransmission in mammalian spinal cord.
Authors: Hunanyan Arsen , Garcia-Alias Guillermo , Levine Joel , Fawcett James , Mendell Lorne , Arvanian Victor 
Published: July 2019

AbstractChronic unilateral hemisection (HX) of the adult rat spinal cord diminishes conduction through intact fibers in the ventrolateral funiculus (VLF) contralateral to HX. Intraspinal injections of Chondroitinase-ABC, known to digest chondroitin sulfate proteoglycans (CSPGs) in the vicinity of injury, prevented this decline of axonal conduction. This was associated with improved locomotor function. We further injected three purified CSPGs into the lateral column of the uninjured cord at T10: NG2 and neurocan, which increase in the vicinity of a spinal injury, and aggrecan, which decreases. Intraspinal injection of NG2 acutely depressed axonal conduction through the injection region in a dose dependent manner. Similar injections of saline, aggrecan, or neurocan had no significant effect. These results identify a novel acute action of CSPGs on axonal conduction in spinal cord, and suggest that antagonism of proteoglycans reverses or prevents the decline of axonal conduction, in addition to stimulating axonal growth.
Discovery of multiple lead compounds as M2 inhibitors through the focused screening of a small primary amine library.
Authors: Hu Wenhui , Zeng Shaogao , Li Chufang , Jie Yanling , Li Zhiyuan , Chen Ling 
Published: July 2019

AbstractThe discovery of new anti-influenza drugs is urgent, particularly considering the recent threat of swine flu. In this study, the influenza virus M2 protein was expressed in HEK293 cells and shown to have selective ion channel activity for monovalent ions. The anti-influenza virus drug amantadine hydrochloride significantly attenuated the inward current induced by hyperpolarization of HEK293 cell membranes. Although adamantine derivatives are the only M2 drugs for influenza virus A, their use is limited in the US due to drug resistance. Here we report the discovery of multiple M2 inhibitor lead compounds that were rapidly generated through focused screening of a small primary amine library. The screen was designed using a scaffold-hopping strategy based on amantadine. This study suggests that an antiviral compound directed against a conserved motif may be more useful than amantadine in inhibiting viral replication.
Modeling the hydrolysis of perfluorinated compounds containing carboxylic and phosphoric acid ester functions, alkyl iodides, and sulfonamide groups
Authors: Rayne Sierra , Forest Kaya 
Published: July 2019

AbstractTemperature dependent rate constants were estimated for the acid- and base-catalyzed and neutral hydrolysis reactions of perfluorinated telomer acrylates (FTAcrs) and phosphate esters (FTPEs), and the SN1 and SN2 hydrolysis reactions of fluorotelomer iodides (FTIs). Under some environmental conditions, hydrolysis of monomeric FTAcrs could be rapid (half-lives of several years in marine systems and as low as several days in some landfills) and represent a dominant portion of their overall degradation. Abiotic hydrolysis of monomeric FTAcrs may be a significant contributor to current environmental loadings of fluorotelomer alcohols (FTOHs) and perfluoroalkyl carboxylic acids (PFCAs). Polymeric FTAcrs are expected to be hydrolyzed more slowly, with estimated half-lives in soil and natural waters ranging between several centuries to several millenia absent additional surface area limitations on reactivity. Poor agreement was found between the limited experimental data on FTPE hydrolysis and computational estimates, requiring more detailed experimental data before any further modeling can occur on these compounds or their perfluoroalkyl sulfonamidoethanol phosphate ester (PFSamPE) analogs. FTIs are expected to have hydrolytic half-lives of about 130 days in most natural waters, suggesting they may be contributing to substantial FTOH and PFCA inputs in aquatic systems. Perfluoroalkyl sulfonamides (PFSams) appear unlikely to undergo abiotic hydrolysis at the S-N, C-S, or N-C linkages under environmentally relevant conditions, although potentially facile S-N hydrolysis via intramolecular catalysis by ethanol and acetic acid amide substituents warrants further investigation.
Computational binding mechanism of Mycobacterium tuberculosis UDP-NAG enolpyruvyl transferase (MurA) with inhibitors fosfomycin, cyclic disulfide analog RWJ-3981, pyrazolopyrimidine analog RWJ-110192, purine analog RWJ-140998, 5-sulfonoxy-anthranilic aci
Authors: Anuradha C. M. , Babajan B. , Chaitanaya M. , Rajasekhar C. , Chitta Suresh Kumar 
Published: July 2019

AbstractWorldwide, tuberculosis (TB) remains the most frequent and important infectious disease causing morbidity and death. One-third of the world's population is infected with Mycobacterium tuberculosis (Mtb), the etiologic agent of TB. In this context, TB is in the top three, with malaria and HIV being the leading causes of death from a single infectious agent, and about two million deaths are attributable to TB annually. The bacterial enzyme MurA catalyzes the transfer of enolpyruvate from phosphoenolpyruvate (PEP) to uridine diphospho-N-acetylglucosamine (UNAG), which is the first committed step of bacterial cell wall biosynthesis. In this work, 3D structural model of Mtb-MurA enzyme has been developed, for the first time, by homology modeling and molecular dynamics simulation techniques. The model provided clear insight in its structure features, i.e. substrate binding pocket, and common docking site. Multiple sequence alignment and 3D structure model provided the putative substrate binding pocket of Mtb-MurA with respect to E.coli MurA. This analysis was helpful in identifying the binding sites and molecular function of the MurA homologue. Molecular docking study was performed on this 3D structural model, using different classes of inhibitors like fosfomycin, cyclic disulfide analog RWJ-3981, pyrazolopyrimidine analog RWJ-110192, purine analog RWJ-140998, 5-sulfonoxy-anthranilic acid derivatives T6361, T6362 and the results showed that the 5-sulfonoxyanthranilic acid derivatives is showed best interaction compared with other inhibitor, taking in to this we also design a new efficient analogs of T6361 and T6362 which are showed even better interaction with Mtb-MurA than the parental5-sulfonoxy-anthranilic acid derivatives. Further the comparative molecular electrostatic potential and cavity depth analysis of Mtb-MurA suggested several important differences in its substrate and inhibitor binding pocket. Such differences could be exploited in the future for designing of a more specific inhibitor for Mtb-MurA enzyme
An illusion induced by an illusion -perceptual filling-in of coloured negative afterimages
Authors: Geremek Adam , Hamburger Kai , Spillmann Lothar 
Published: July 2019

AbstractVisual filling-in relates to a perceptual phenomenon in which a stimulus pattern apparently undergoes dynamic changes assuming an attribute such as colour, texture, or brightness from the surround. This perceptual completion effect has up to now been shown only for real images. Here, we present filling-in in negative afterimages, a phenomenon not yet reported. Using coloured disk-ring patterns for stimuli, we demonstrate that afterimage filling-in arises independently, and is not simply a replica of filling-in observed in real images. Such filling-in does not occur when the afterimage is elicited dichoptically, suggesting its emergence within the monocular visual pathway. In this way, our findings indicate that filling-in under certain conditions may derive from an active neural mechanism located at low levels of the visual pathway.
Interventions to Promote Cancer Awareness and Early Presentation: Systematic Review
Authors: Austoker J , Bankhead C , Forbes Lindsay , Atkins L , Martin F , Robb K , Wardle J , Ramirez A 
Published: July 2019

AbstractLow cancer awareness contributes to delay in presentation for cancer symptoms and may lead to delay in cancer diagnosis. The aim of this study was to review the evidence for the effectiveness of interventions to raise cancer awareness and promote early presentation in cancer to inform policy and future research. We searched bibliographic databases and reference lists for randomised controlled trials of interventions delivered to individuals, and controlled or uncontrolled studies of interventions delivered to communities. We found some evidence that interventions delivered to individuals modestly increase cancer awareness in the short term and insufficient evidence that they promote early presentation. We found limited evidence that public education campaigns reduce stage at presentation of breast cancer, malignant melanoma and retinoblastoma.
Mega- change gene copies are produced by reverse transcription of precursor RNA with replaced introns.
Authors: Schwartz Drew 
Published: July 2019

AbstractThis report describes the presence of copy genes in plants where the sequence similarity to their parental genes is almost completely limited to limited to the exons. Evidence is presented that indicates that they arose via a novel processing of transcribed precursor RNA during which the introns are replaced rather than excised, followed by reverse transcription and incorporation into the chromosomes. Intron replacement may play an important role in evolution as it results in megagene changes.
An offside position in football cannot be detected in zero milliseconds
Authors: Belda Maruenda Francisco 
Published: July 2019

AbstractErrors when judging an offside position in football are very frequent. In the last years, several scientific papers have tried to explain the causes for human errors. When a referee or an assistant referee misjudges an offside position, it is thought to be caused by a human error. A human error means to carry out incorrectly an action we are physiologically qualified for. The hypothesis to be studied in this paper is if when judging an offside position it is possible to attribute errors to humans or to the fact that human physiology and the technical media are not capable of detecting an offside position. The offside rule has to be applied in real time, in zero milliseconds, in the precise moment when the ball is being passed, never 1 millisecond or even 1 millionth of a second later. This paper shows that the human being and the technological media are both physically and technically incapable of detecting an offside position in real time, in zero milliseconds. The results of this study show that when the ball is passed, the human eye and brain and the technological media need some time to locate the at least four players who intervene in an offside position. When those players are located, time has passed and they are never in the original position, when the ball was passed. Football players are trained for speed and acceleration to change their geographical position in the field when the ball is passed. Therefore, we cannot refer to a human error when an offside position is misjudged. The human being and the technological media will never be capable of detecting an offside position in real time, in zero milliseconds. The key of the offside position is a physical problem: time. The IFAB must abolish the offside rule.
Theoretical studies on the pK~a~ values of perfluoroalkyl carboxylic acids: Non-helical conformation acidity constants for n-perfluorooctanoic acid (n-PFOA)
Authors: Rayne Sierra , Forest Kaya 
Published: July 2019

AbstractA molecular mechanics force field method (MMFF94) systematic rotor conformational search was conducted on the well known environmental contaminant n-perfluorooctanoic acid (n-PFOA). The MMFF94 conformational search yielded 2915 separate low- through high-energy conformers of n-PFOA. Ranking of these structures gave the 94 lowest MMFF94 energy conformations that were subjected to subsequent density functional theory (DFT) computational investigations at the B3LYP/6-311++G(d,p) level of theory. Application of a thermodynamic cycle approach, coupled with aqueous and gas phase DFT calculations on the molecular and anionic forms for each of the 94 lowest energy n-PFOA conformers, gave estimated acidity constants (pK~a~ values) for a final converged set of twelve n-PFOA conformers, including the global minimum helical perfluoroalkyl chain geometry and eleven non-helical higher energy conformations. Collectively, the twelve lowest energy conformers appear to encompass 85% of the total conformational space for n-PFOA, indicating no higher energy conformations likely remain that could appreciably influence the observed composite aqueous pK~a~ of this compound. The estimated pK~a~ values of all eleven non-helical n-PFOA conformers were within 0.2 pK~a~ units of the helical conformer pK~a~. The findings support previous predictions and recent experimental evidence for an aqueous phase n-PFOA monomeric pK~a~ of about zero.
A Unifying Scenario on the Origin and Evolution of Cellular and Viral Domains
Authors: Bandea Claudiu 
Published: July 2019

AbstractThe cellular theory on the nature of life has been one of the first major advancements in biology. Viruses, however, are the most abundant life forms, and their exclusion from mainstream biology and the Tree of Life (TOL) is a major paradox in biology. This article presents a broad, unifying scenario on the origin and evolution of cellular and viral domains that challenges the conventional views about the history of life and supports a TOL that includes viruses. Co-evolution of viruses and their host cells has led to some of the most remarkable developments and transitions in the evolution of life, including the origin of non-coding DNA as a genomic protective device against viral insertion damage. However, one of the major fundamental evolutionary developments driven by viruses was probably the origin of cellular domains - Bacteria, Archaea and Eukarya - from the Last Universal Common Ancestor (LUCA) lineage, by evolving anti-fusion mechanisms. Consistent with a novel fusion/fission model for the population mode of evolution of LUCA, this paper presents a “cell-like world” model for the origin of life. According to this model the evolution of coupled replication, transcription and translation system (RT&T) occurred within non-living cell-like compartments (CCs). In this model, the ancestral ribosome originated as template-based RNA synthesizing machinery. The origin of the cellular genome as a centralized unit for storage and replication of genetic information within the CCs facilitated the evolution of the ancestral ribosome into a powerful translation machinery - the modern ribosome. After several hundred millions of years of providing an enclosed environment and fusion/fission based exchanges necessary for the population mode of evolution of the basic metabolism and the RT&T, the CCs evolved into the first living entities on earth - the LUCA lineage. The paper concludes with a proposal for a TOL that integrates the co-evolution of cellular and viral domains. This is one of a series of three articles that present a unifying scenario on the origin and evolution of viral and cellular domains, including the origin of life, which has significant t bio-medical implications and could lead to a significant paradigm shift in biology.
No evidence for a recent genetic bottleneck in the endangered Sheko cattle breed (African Bos taurus) revealed by microsatellite analysis
Authors: Dadi Hailu , Mwacharo Joram , Tibbo Markos , Takahashi Yukimizu , Nomura Koh , Hanada Hirofumi , Amano Takashi 
Published: July 2019

AbstractSheko is African taurine cattle, valued for its milk yield, adaptation to humid tsetse infested environment and trypanotolerance. We used 30 microsatellite markers in analyzing 30 DNA samples. We found high genetic diversity and no genetic bottlenecks in endangered Sheko cattle. Sheko cattle have not undergone recent genetic bottlenecks, in spite of drastic reduction in its overall demographic population size. The results were supported by three statistical methods: (i) detection of heterozygosity excess (ii) a mode-shift indicator of allele distribution pattern (iii) the ratio of the number of alleles to the range of allele size, M-ratio test. This breed reflects historical and cultural identity of local communities and represents a unique component of the global domestic animal biodiversity that deserve priority for conservation.
Are endocannabinoid type 1 receptor gene (CNR1) polymorphisms associated with obesity and metabolic syndrome in postmenopausal Polish women?
Authors: Dunajska Katarzyna , Lwow Felicja , Jedrzejuk Diana , Milewicz Andrzej , Tworowska-Bardzinska Urszula , Laczmanski Lukasz 
Published: July 2019

Abstract
Objective:
The aim of this study was to determine whether genetic variation at the cannabinoid receptor-1 (CNR1) locus could have an effect on adiposity, fat distribution and obesity-related metabolic disorders in Polish postmenopausal women.Design and Subjects: The A3813G, G1422A and A4895G single nucleotide polymorphisms of CNR1 were genotyped in 348 randomly selected postmenopausal women aged 50-60 years recruited from the Wroclaw city population. Measurements: CNR1 genotypes, anthropometric measures (BMI, WC, body fat distribution by DEXA) and metabolic parameters (glucose, lipid profile, insulin FIRI) were determined.

Results:
The 3813G allele was not significantly associated with higher body mass, BMI, WC, total fat, or fat percentage, but was associated with higher android fat deposit (2971.78 &177; 1655.08 &177; 2472.64 &177; 1300.53, p = 0.007) and percentage of android fat (37.59 &177; 8.45 vs. 35.66 &177; 7.63, p = 0.062). The 1422A allele was associated with higher total fat (31587.72 &177; 9161.28 g vs. 26078.26 &177; 7552.14 g, p = 0.019), fat percentage (40.51 &177; 5.66% vs. 37.51 &177; 4.99%, p = 0.052), and percentage of android fat (40.86 &177; 9.73% vs. 36.09 &177; 7.70%, p = 0.047). No associations were observed for the A4895G variant.

Conclusions:
There is an association of variants of CNR1 with obesity-related phenotypes in Polish postmenopausal women. As CB1 is a drug target for obesity, pharmacogenetic receptor gene analysis of obesity treatment by endocannabinoid blockade may be of interest to identify the best responders.
Oxidation numbers as Social Security Numbers: Are they predictive or postdictive?
Authors: Raebiger Hannes , Lany Stephan , Resta Raffaele , Zunger Alex 
Published: July 2019

AbstractThe Oxidation Number (ON) of an atom within a molecule or solid is a well defined quantity in chemistry (assuming a consistent set of rules are followed), with a long and distinguished history of usefulness. The question revisited recently [1–3] is whether it carries a predictive physical meaning in its own right beyond being an unquestionably convenient label. For example, whereas the color of compounds physically reflects the relative energetic positions of occupied vs. unoccupied, dipolecoupled energy levels, can the color be explained [4] by the oxidation state of the central ion? Can the different colors of various Mn compounds be predicted or explained in terms of their oxidation numbers [e.g. pink Mn(II) vs. black Mn(IV) vs. purple Mn(VII)], or does such understanding entail knowledge of the occupancy of the hybridized d bands, a knowledge not provided by the ON (but possibly labeled by it, once such understanding is independently acquired)? Also, the photoemission core shifts of an atom within a molecule (e.g. relative to a reference of the atom in its elemental form) physically represent the balance of all electrostatic charges in the system as felt by that atomic site. Can this balance be predicted or explained [1] by the oxidation number of the ion, or is the latter only a convenient short-hand notation (often assigned ex post facto) for an otherwise possibly nontrivial electronic structure? In other words, the central question here is whether the Oxidation Number is predictive, in its own right, or does it act functionally as a Social Security Number that conveniently labels a person, but by itself (e.g., without additional access to financial, medical, or educational records, or psychoanalysis) does not lead to understanding of the person.
Ciproxifan, an H~3~ Receptor Antagonist, Improves Learning and Memory in the APP Mouse Model of Alzheimer's Disease
Authors: Bardgett Mark , Davis Natasha , Griffith Molly 
Published: July 2019

AbstractMice that express the mutant form of the human amyloid precursor gene associated with early-onset familial Alzheimer's disease demonstrate memory deficits and amyloid plaques. We show here that ciproxifan, a prototypical antagonist of H~3~-type histamine receptors, alleviates two types of learning and memory impairments in such mice. These data support the idea that modulation of H~3~ receptors represents a viable therapeutic strategy in the treatment of Alzheimer's disease.