bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying the Polo® mint mandibular third molar: a case series
Authors: Chopra R. , Patel D. , Sproat C. , Patel V.
Published: November 2018

Aim

Perforation of mandibular third molars (MTMs) by the inferior dental nerve (IDN) is an uncommon finding. Such cases are thought to carry the highest risk for IDN injury (IDNI) due the entrapment of the nerve within the tooth. This case series aims to highlight the lack of consistency through varying radiographic signs, a perforated MTM may present on 2D imaging.

Methods

In this series, 22 cases of perforated MTMs were identified prospectively by cone beam CT. The plain film radiographic images for these cases were retrospectively analysed to determine if any of the 2D radiographic features could help to identify a perforated MTM.

Results

In 86% (19/22) of the cases at least three IDNI ‘at risk' radiographic signs were present, 91% (20/22) of the cases superimposition of the IDN canal was seen and in 86% (19/22) of the cases banding of the root was evident. Deviation and narrowing of the canal was only identified in 59% (13/22) of the cases.

Conclusion

In this study no single or repeated multiple 2D ‘at risk' sign was predictive of perforation of the tooth by the IDN. Most cases show multiple ‘at risk' signs but there remains no consistency even within these signs.
The Moral Economy of Neoliberalism: How Voters Use Neoliberal Ideology to (De)Legitimate Undocumented Worker Access to Labor Markets
Authors: Vila‐Henninger Luis
Published: November 2018

Neoliberalism is prevalent in American life. While researchers have documented the use of neoliberal ideology in institutional and macrolevel policy contexts, they have yet to investigate how voters use neoliberal ideology to legitimate their position on economic policy. I use data from semi‐structured interviews with 85 Tucsonans about why they voted the way they did on Proposition 202 (2008): “Arizona Stop Illegal Hiring”—which sought to reregulate undocumented worker labor market access—to address this gap. I found evidence of two distinct neoliberal ideological legitimations: “fair market competition” and “individual responsibility.” Furthermore, I use these data to shed light on the debate over whether neoliberalism spans partisan affiliation or converges with American conservatism. I found that voters across party lines who supported the measure paired neoliberal legitimations with conservative legitimations. We can interpret this bipartisan use of neoliberal ideology as evidence of a neoliberal “moral economy”—or consensus about the moral principles in which market action is embedded. Evidence of this moral economy indicates that moral principles from neoliberal ideology are simultaneously bipartisan and converge with American conservatism. These findings suggest that there could be a broader moral consensus among voters concerning the legitimacy of anti‐immigration economic policies.
An improved measuring method for the information entropy of network topology
Authors: Li Wenjing , Hu Dan , Liu Yi
Published: November 2018

The measurement of network topologies is of great significance to the multi‐scale expression and generalization of maps. The problem encountered in existing metrics is whether to use the approach of measuring a single type of information or measuring the overall information; however, redundancy can be calculated. In view of these problems, this article selects three types of information metrics that express compactness, heterogeneity, and discreteness in a network topology. The measurement model has been simplified, and the calculation has been improved. By comparing various methods and measuring the information entropy of area road networks, the simplicity and validity of the improved method are verified.
A spatial‐adjacency‐based approach for analyzing urban landscape structure
Authors: Jin Rui , Gong Jianya , Deng Min , Wan Yiliang , Yang Wentao
Published: November 2018

Rapid urbanization can cause remarkable and high fragmentation of urban landscapes, which will affect the function and services of landscapes and result in a series of ecological and environmental problems. To identify the spatial structure and explore the effects of internal features on this structure, we propose a spatial‐adjacency‐based method for interactions between urban main roads (main road corridors) and the urban landscape. Dongguan was used as the research area, for the sample period 1997–2013. Urban land patches were analyzed comprehensively, based on the spatial relationship with main roads, and according to landscape indices and landscape gradients. Furthermore, to explore the overall spatial attraction and spillover effects of the main road corridors, an extended Voronoi‐based spatial‐adjacency measuring index (EVSAI) was proposed to measure geographic adjacency. Finally, we established one complete set of classification criteria relevant to the changing patterns of the spatial structure. The experimental results indicated a dense network of main road corridors in the regions adjacent to the central area of Dongguan. The findings further revealed that the landscape pattern experienced three stages of spatiotemporal changes spanning the 16 years: central sprawl (1997–2005), peripheral sprawl (2005–2009), and central sprawl (2009–2013).
Vaginal estrogen deficiency
Authors: Khanjani Shirin , Panay Nick
Published: November 2018

Key content

Vaginal estrogen deficiency occurs with declining serum estradiol levels in menopause and premature ovarian insufficiency.

The symptoms most commonly involve vulval and vaginal dryness, pruritis, dyspareunia and discharge.

Treatment is simple and easily accessible and can be hormonal and nonhormonal.

Nonhormonal treatments are particularly helpful for women who cannot take estrogen. They include simple treatments such as local lubricants and moisturisers, and newer modalities of treatment, including laser.

Vaginal estrogen is the most commonly used form of hormonal treatment. However, selective estrogen receptor modulators, tissue‐selective estrogen complexes, androgens and dehydroepiandrosterone have recently been introduced and are effective and safe.

Learning objectives

To understand the pathogenesis, symptoms and diagnosis of vulvovaginal atrophy.

To appreciate attitudes and stances towards vulvovaginal atrophy.

To understand management options for vaginal estrogen deficiency.

Ethical issues

The impact of vulvovaginal atrophy on the quality of life of many women is profound but underestimated.

Vulvovaginal atrophy is underdiagnosed and undertreated.

Considering that more women are spending a significant proportion of their lives in the postmenopausal period, understanding the diagnosis and treatment of vulvovaginal atrophy must develop in synchrony with this growing unmet need.
Translational dynamics of individual microbubbles with millisecond scale ultrasound pulses
Authors: Acconcia Christopher N. , Wright Alex , Goertz David E.
Published: November 2018

It is established that radiation forces can be used to transport ultrasound contrast agents, particularly for molecular imaging applications. However, the ability to model and control this process in the context of therapeutic ultrasound is limited by a paucity of data on the translational dynamics of encapsulated microbubbles under the influence of longer pulses. In this work, the translation of individual microbubbles, isolated with optical tweezers, was experimentally investigated over a range of diameters (1.8–8.8 μm, n = 187) and pressures (25, 50, 100, 150, and 200 kPa) with millisecond pulses. Data were compared with theoretical predictions of the translational dynamics, assessing the role of shell and history force effects. A pronounced feature of the displacement curves was an effective threshold size, below which there was only minimal translation. At higher pressures (≥150 kPa) a noticeable structure emerged where multiple local maxima occurred as a function of bubble size. The ability to accurately capture these salient features depended on the encapsulation model employed. In low Reynolds number conditions (i.e., low pressures, or high pressures, off-resonance) the inclusion of history force more accurately fit the data. After pulse cessation, bubbles exhibited substantial displacements consistent with the influence of history effects.
The HDAC3–SMARCA4–miR-27a axis promotes expression of the
PAX3:FOXO1
fusion oncogene in rhabdomyosarcoma
Authors: Bharathy Narendra , Berlow Noah E. , Wang Eric , Abraham Jinu , Settelmeyer Teagan P. , Hooper Jody E. , Svalina Matthew N. , Ishikawa Yoshihiro , Zientek Keith , Bajwa Zia , Goros Martin W. , Hernandez Brian S. , Wolff Johannes E. , Rudek Michelle A. , Xu Linping , Anders Nicole M. , Pal Ranadip , Harrold Alexandria P. , Davies Angela M. , Ashok Arya , Bushby Darnell , Mancini Maria , Noakes Christopher , Goodwin Neal C. , Ordentlich Peter , Keck James , Hawkins Douglas S. , Rudzinski Erin R. , Chatterjee Bishwanath , Bächinger Hans Peter , Barr Frederic G. , Liddle Jennifer , Garcia Benjamin A. , Mansoor Atiya , Perkins Theodore J. , Vakoc Christopher R. , Michalek Joel E. , Keller Charles
Published: November 2018

The HDAC inhibitor entinostat sensitizes a subset of rhabdomyosarcomas to chemotherapy.
Identification of a Novel Gene Associated with High-Level β-Lactam Resistance in Heterogeneous Vancomycin-Intermediate Staphylococcus aureus Strain Mu3 and Methicillin-Resistant S. aureus Strain N315
Authors: Matsuo Miki , Yamamoto Norio , Hishinuma Tomomi , Hiramatsu Keiichi
Published: November 2018

β-Lactam resistance levels vary among methicillin-resistant
Staphylococcus aureus
(MRSA) clinical isolates, mediated by chromosomal mutations and exogenous resistance gene
mecA
. However, MRSA resistance mechanisms are incompletely understood.
Inhibitors of Signaling Pathways That Block Reversal of HIV-1 Latency
Authors: Vargas Benni , Giacobbi Nicholas S. , Sanyal Anwesha , Venkatachari Narasimhan J. , Han Feng , Gupta Phalguni , Sluis-Cremer Nicolas
Published: November 2018

Signaling pathways play a key role in HIV-1 latency. In this study, we used the 24ST1NLESG cell line of HIV-1 latency to screen a library of structurally diverse, medicinally active, cell permeable kinase inhibitors, which target a wide range of signaling pathways, to identify inhibitors of HIV-1 latency reversal.
Barriers to 3-Hydroxypropionate-Dependent Growth of Rhodobacter sphaeroides by Distinct Disruptions of the Ethylmalonyl Coenzyme A Pathway
Authors: Carlson Steven J. , Fleig Angela , Baron M. Kelsey , Berg Ivan A. , Alber Birgit E.
Published: November 2018

Mutant analysis is an important tool utilized in metabolic studies to understand which role a particular pathway might have under certain growth conditions for a given organism. The importance of the enzyme and of the pathway in which it participates is discretely linked to the resulting phenotype observed after mutation of the corresponding gene. This work highlights the possibility of incorrectly interpreting mutant growth results that are based on studying a single unit (gene and encoded enzyme) of a metabolic pathway rather than the pathway in its entirety. This work also hints at the possibility of using an enzyme as a drug target although the enzyme may participate in a nonessential pathway and still be detrimental to the cell when inhibited.
Draft Genome Sequences of Salmonella enterica subsp.
enterica
Serotype Heidelberg from Chicken and Turkey Farm Environments
Authors: Deblais Loïc , Scaria Joy , Rajashekara Gireesh
Published: November 2018

Thirty-one different
Salmonella enterica
subsp.
enterica
serotype Heidelberg isolates collected from several chicken- and turkey-associated farm environments in the Midwestern United States were analyzed using whole-genome sequencing.
Complete Genome Sequence of Lactobacillus reuteri SKKU-OGDONS-01, Isolated from a Chicken’s Small Intestine
Authors: Kim Dongjun , Cho Mun-ju , Cho Seungchan , Lee Yongjun , Byun Sung June , Lee Sukchan
Published: November 2018

Lactobacillus reuteri
SKKU-OGDONS-01 is a potentially indigenous probiotic strain isolated from the small intestine of a 27-week-old chicken. The complete genome of
L. reuteri
SKKU-OGDONS-01 comprises a single circular chromosome.
Draft Genome Sequence of
Pseudomonas
sp. LS-2, Isolated from a Diseased
Gastrodia elata
Plant
Authors: Li Xiangyang , Zou Xuefeng , Zhang Kaishuang , Meng Huaixin , Shi Dingxiang
Published: November 2018

We report here the draft genome sequence of
Pseudomonas
sp. LS-2, isolated from the decaying aerial stem of a
Gastrodia elata
plant.
Glycerol Monolaurate (GML) and a Nonaqueous Five-Percent GML Gel Kill
Bacillus
and
Clostridium
Spores
Authors: Schlievert Patrick M. , Kilgore Samuel H. , Kaus Gabriela M. , Ho Theresa D. , Ellermeier Craig D.
Published: November 2018

Bacillus
and
Clostridium
spores are known to be highly resistant to killing, persisting on environmental and human body surfaces for long periods of time. In favorable environments, these spores may germinate and cause human diseases. It is thus important to identify agents that can be used on both environmental and human skin and mucosal surfaces and that are effective in killing spores. We previously showed that the fatty acid monoester glycerol monolaurate (GML) kills stationary-phase cultures of
Bacillus anthracis
. Since such cultures are likely to contain spores, it is possible that GML and a human-use-approved GML nonaqueous gel would kill
Bacillus
and
Clostridium
spores. The significance of our studies is that we have identified GML, and, to a greater extent, GML solubilized in a nonaqueous gel, as effective in killing spores from both bacterial genera.
Pressure-induced metallization of condensed-phase RDX: molecular dynamic simulations in conjunction with MSST method
Authors: Bai Zi-Qiu , Chang Jing , Ji Guang-Fu , Ge Ni-Na
Published: November 2018

The anisotropy of impact sensitivity and microscopic electron properties of the cyclotrimethylene trinitramine (C3H6N6O6) (RDX) under shock loading are investigated in our work. The simulation is performed using molecular dynamic (MD) simulations in conjunction with multi-scale shock technique (MSST). By calculating the microscopic electronic properties and combining the thermodynamic properties, we predict that the metallization pressure of the RDX crystal is approximately 170 GPa under shock loading, which is slightly less than the metallization pressure under hydrostatic pressure. We also found that the microscopic electronic properties are related to the impact sensitivity. When the shock loading is along the z direction, the time of the transition from the insulating state to the metallization of the RDX crystal lags behind the shock loading along the x or y direction. Therefore, we predict that the RDX crystal has a lower sensitivity when the shock loading is along the z direction.
Stem- and stand-level growth and mortality following partial cutting in eastern boreal poplar – white spruce stands
Authors: Brais Suzanne , Harvey Brian D. , Bose Arun K.
Published: November 2018

Variable retention (VR) and partial cutting are both considered important silvicultural tools of natural disturbance or ecosystem based forest management approaches. Partial harvesting differs from VR in that post-treatment growth responses and stand regeneration are the primary objective rather than the maintenance of biodiversity. This partial cutting study is undertaken in mixed poplar (Populus spp.) – white spruce (Picea glauca (Moench) Voss) stands in the eastern Canadian boreal mixedwood forest. It compares, at the tree level, absolute growth rates (AGR) and relative growth rates (RGR) of basal area (BA) and stem survival; and at the stand level, it also compares absolute BA growth, mortality, and sapling density 10 years following treatment. The completely randomized experiment was established with four intensities of partial cutting (0, 50%, 65%, and 100% of poplar BA). All partial cutting intensities had a significant and similar positive effect on AGR of residual spruce stems. Complete poplar removal resulted not only in the highest increase in RGR of suppressed and intermediate spruce stems, but also in higher spruce mortality. Removal of 50% of the initial poplar stand BA provided the best trade-off between positive residual stem growth of spruce and poplar and limited post-treatment mortality.
On the origin and nature of dark matter
Authors: Frampton P. H.
Published: November 2018

It is discussed how the ideas of entropy and the second law of thermodynamics, conceived long ago during the nineteenth century, underly why cosmological dark matter exists and originated in the first three years of the universe in the form of primordial black holes, a very large number of which have many solar masses including up to the supermassive black holes at the centres of galaxies. Certain upper bounds on dark astrophysical objects with many solar masses based on analysis of the CMB spectrum and published in the literature are criticised. For completeness we discuss WIMPs and axions which are leading particle theory candidates for the constituents of dark matter. The PIMBHs (Primordial Intermediate Mass Black Holes) with many solar masses should be readily detectable in microlensing experiments which search the Magallenic Clouds and measure light curves with durations of from one year up to several years.
Resonant detection and production of axions with atoms
Authors: Flambaum V. V. , Tran Tan H. B. , Samsonov I. B. , Stadnik Y. V. , Budker D.
Published: November 2018

The axions and axion-like particles can be detected via a resonant atomic or molecular transition induced by axion absorption. The signal obtained in this process is second order in the axion-electron interaction constant and hence small. In this chapter, it is demonstrated that this signal may become first order in the axion-electron interaction constant if we allow the interference between the axion-induced transition amplitude and the transition amplitude induced by the electromagnetic radiation. Additionally, we show that the conventional scheme of producing axions from photons in a magnetic field may be improved if the field is replaced by an atomic medium in which photons scattering off the atoms in the forward direction are transformed into axions.
Acoustic scattering by cylinders immersed in a fluid medium: Modeling, solving and verifying
Authors: Chu Jing , Han Qingbang
Published: November 2018

The shear waves have been taken into consideration to deduce the theoretical model of the scattering of isotropic circular solid cylinders in a fluid medium. The theoretical analysis has been done based on the wave equation and the three classical boundary conditions. The analytical solution of the far-field pattern for this scattering issue has been derived and the pressure in the scattered wave can be given. And the finite element method (FEM) has been used to solve the underwater acoustic scattering problems. Numerical solution of the resulting was discussed in three directions. The following work is to study the scattering problems of collection of cylinders with arbitrary cross-sections and any numbers. The conclusions drawn in this paper could contribute to explore the acoustic propagation characteristics of the two-phase media.
STATISTICS OF VIX FUTURES AND APPLICATIONS TO TRADING VOLATILITY EXCHANGE-TRADED PRODUCTS
Authors: AVELLANEDA M. , PAPANICOLAOU A.
Published: November 2018

We study the dynamics of VIX futures and ETNs/ETFs. We find that contrary to classical commodities, VIX and VIX futures exhibit large volatility and skewness, consistent with the absence of cash-and-carry arbitrage. The constant-maturity futures (CMF) term-structure can be modeled as a stationary stochastic process in which the most likely state is contango with VIX [Formula: see text] and a long-term futures price [Formula: see text]. We analyze the behavior of ETFs and ETNs based on constant-maturity rolling futures strategies, such as VXX, XIV and VXZ, assuming stationarity and through a multi-factor model calibrated to historical data. We find that buy-and-hold strategies consisting of shorting ETNs that roll long futures, or buying ETNs that roll short futures, will produce theoretically-sure profits if it is assumed that CMFs are stationary and ergodic. To quantify further, we estimate a 2-factor lognormal model with mean-reverting factors to VIX and CMF historical data from 2011 to 2016. The results confirm the profitability of buy-and-hold strategies, but also indicate that the latter have modest Sharpe ratios, of the order of [Formula: see text] or less, and high variability over 1-year horizon simulations. This is due to the surges in VIX and CMF backwardations which are observed sporadically in the volatility futures market.
TIIE-28 Swaps as Risk-Adjusted Forecasts of Monetary Policy in Mexico
Authors: García-Verdú Santiago , Ramos-Francia Manuel , Sánchez-Martínez Manuel
Published: November 2018

Information extracted from financial derivatives on interest rates is commonly used to forecast movements in interest rates. However, such an extraction generally assumes that agents are risk-neutral, which is not necessarily the case. Accordingly, it might be useful to account for the agents’ risk-aversion when doing these forecasts, which one can implement by adding a risk-correction. In this context, we use TIIE-28 swaps to forecast changes in monetary policy in Mexico, using a set of financial variables to account for the risk-correction. We assess whether models with a risk-correction outperform the TIIE-28 swaps rates, and find that the in-sample explained variability improves when using a risk-correction. Centrally, we document that our main model’s out-of-sample forecasts are similar for short horizons (3-month), and statistically significantly better for longer horizons (9 to 24-month), compared to the direct use of TIIE-28 swaps interest rates.
Chronology of the Saxothuringian subduction in the West Sudetes (Bohemian Massif, Czech Republic and Poland)
Authors: Konopásek Jiří , Anczkiewicz Robert , Jeřábek Petr , Corfu Fernando , Žáčková Eliška
Published: November 2018

Isotopic dating of monazite and garnet from high-pressure metamorphic rocks exposed in the northern part of the Saxothuringian palaeo-suture in the Bohemian Massif revealed a diachronous metamorphism of various rock types that are now closely associated within allochthonous units representing the Devonian–Carboniferous subduction–accretionary complex. Mafic blueschists of the middle unit yielded a Lu–Hf garnet age of 363.9 ± 1.3 Ma. The blueschists occur within high-pressure, garnet-free phyllites. Monazite extracted from this rock type yielded a U–Pb isotope dilution thermal ionization mass spectrometry age of 336.5 ± 0.5 Ma. Garnet-bearing micaschist of the lower unit contains monazite with a U–Pb secondary ion mass spectrometry age of 341 ± 3 Ma, consistent with Lu–Hf garnet–whole-rock ages of 344.5 ± 1.3 and 342 ± 7 Ma obtained from the same rock type. Existing tectonic models of the Bohemian Massif, and particularly of its northern part, assume that the period of oceanic subduction was terminated at
c.
380–375 Ma by the arrival of an attenuated Saxothuringian continental crust, which was partly subducted and partly relaminated underneath the overriding Teplá–Barrandian Domain. However, our data, as well as data from mafic high-pressure rocks in the southern part of the Saxothuringian Domain, suggest that the initial collision was probably caused by the arrival of a smaller crustal block present within the Saxothuringian oceanic domain. After its subduction and relamination, the oceanic subduction was re-established and terminated by continental subduction and later collision of the Saxothuringian passive margin at
c.
345–335 Ma.
An Empirical Investigation on the Benefits of Gamification in Programming Courses
Authors: Marín B. , Frez J. , Cruz-Lemus J. , Genero M.
Published: November 2018

Context: Programming courses are compulsory for most engineering degrees, but students’ performance on these courses is often not as good as expected. Programming is difficult for students to learn, given that it includes a lot of new, complex, and abstract topics. All of this has led experts to the conclusion that new teaching techniques are required if students are to be motivated and engaged in learning on programming courses. Gamification has come to be an effective technique in education in general, and is especially useful in programming courses. This motivated us to develop an open source gamified platform, called UDPiler, for use in a programming course.

Objective: The main goal of this article is to obtain empirical evidence on the improvement of students’ learning performance when using UDPiler in comparison to a non-gamified compiler.

Method: A quasi-experiment was performed with two groups of first-year engineering students at Diego Portales University in Chile, using a non-gamified compiler and a gamified platform, respectively.

Results: The results reveal that the students obtained better marks when the gamified platform was used to learn C programming. In addition, there is statistical significance in favor of there being a positive effect on the learning performance of those students who used the gamified platform.

Conclusions: The results allow us to conclude that gamification is an encouraging approach with which to teach C programming, a finding that is aligned with previous empirical studies concerning gamification on programming courses, carried out in academic contexts. Nonetheless, we are aware that further validation is also required to corroborate and strengthen the findings obtained and to investigate whether the kind of gamified elements (mechanics, dynamics, and aesthetics) used have any influence on students’ performance, among other issues that deserve further investigation and that are explained throughout this article.
Survey on Computational Trust and Reputation Models
Authors: Braga Diego De Siqueira , Niemann Marco , Hellingrath Bernd , Neto Fernando Buarque De Lima
Published: November 2018

Over the recent years, computational trust and reputation models have become an invaluable method to improve computer-computer and human-computer interaction. As a result, a considerable amount of research has been published trying to solve open problems and improving existing models. This survey will bring additional structure into the already conducted research on both topics. After recapitulating the major underlying concepts, a new integrated review and analysis scheme for reputation and trust models is put forward. Using highly recognized review papers in this domain as a basis, this article will also introduce additional evaluation metrics to account for characteristics so far unstudied. A subsequent application of the new review schema on 40 top recent publications in this scientific field revealed interesting insights. While the area of computational trust and reputation models is still a very active research branch, the analysis carried out here was able to show that some aspects have already started to converge, whereas others are still subject to vivid discussions.
A Survey and Taxonomy of Core Concepts and Research Challenges in Cross-Platform Mobile Development
Authors: Biørn-Hansen Andreas , Grønli Tor-Morten , Ghinea Gheorghita
Published: November 2018

Developing applications targeting mobile devices is a complex task involving numerous options, technologies, and trade-offs, mostly due to the proliferation and fragmentation of devices and platforms. As a result of this, cross-platform app development has enjoyed the attention of practitioners and academia for the previous decade. Throughout this review, we assess the academic body of knowledge and report on the state of research on the field. We do so with a particular emphasis on core concepts, including those of user experience, device features, performance, and security. Our findings illustrate that the state of research demand for empirical verification of an array of unbacked claims, and that a particular focus on qualitative user-oriented research is essential. Through our outlined taxonomy and state of research overview, we identify research gaps and challenges, and provide numerous suggestions for further research.
Relation Extraction Using Distant Supervision
Authors: Smirnova Alisa , Cudré-Mauroux Philippe
Published: November 2018

Relation extraction is a subtask of information extraction where
semantic relationships
are extracted from natural language text and then classified. In essence, it allows us to acquire structured knowledge from unstructured text. In this article, we present a survey of relation extraction methods that leverage pre-existing structured or semi-structured data to guide the extraction process. We introduce a taxonomy of existing methods and describe distant supervision approaches in detail. We describe, in addition, the evaluation methodologies and the datasets commonly used for quality assessment. Finally, we give a high-level outlook on the field, highlighting open problems as well as the most promising research directions.
Acute recovery from disuse atrophy: the role of stretch-activated ion channels in the activation of anabolic signaling in skeletal muscle
Authors: Mirzoev Timur M. , Tyganov Sergey A. , Petrova Irina O. , Shenkman Boris S.
Published: November 2018

The aim of the study was to 1) measure time-course alternations in the rate of protein synthesis (PS) and phosphorylation status of the key anabolic markers, and 2) find out the role of stretch-activated ion channels (SACs) in the activation of anabolic signaling in the rat soleus during an acute reloading following disuse atrophy. Wistar rats were subjected to 14-day hindlimb suspension (HS) followed by 6, 12, and 24 h of reloading. To examine the role of SAC in the reloading-induced activation of anabolic signaling, the rats were treated with gadolinium (Gd3+), a SAC blocker. The content of signaling proteins was determined by Western blot. c-Myc mRNA expression was assessed by RT-PCR. After 24-h reloading, the PS rate was elevated by 44% versus control. After 6-h reloading, the p-70-kDa ribosomal protein S6 kinase (p70S6k) and translation initiation factor 4E-binding protein 1 (4E-BP1) did not differ from control; however, 12-h reloading resulted in an upregulation of both p70s6k and 4E-BP1 phosphorylation versus control. The phosphorylation of AKT (Ser473) and glycogen synthase kinase-3β (Ser9) was reduced after HS and then completely restored by 12-h reloading. c-Myc was significantly upregulated during the entire reloading. Gd3+ treatment during reloading (12 h) prevented a full phosphorylation of p70S6k, rpS6, 4E-BP1, as well as PS activation. The results of the study suggest that 1) enhanced PS during the acute recovery from HS may be associated with the activation of ribosome biogenesis as well as mammalian target of rapamycin complex 1 (mTORC1)-dependent signaling pathways, and 2) functional SACs are necessary for complete activation of mTORC1 signaling in rat soleus during acute recovery from HS.
The effect of PPARγ inhibition on bone marrow adipose tissue and bone in C3H/HeJ mice
Authors: Beekman Kerensa M. , Veldhuis-Vlug Annegreet G. , van der Veen Albert , den Heijer Martin , Maas Mario , Kerckhofs Greet , Parac-Vogt Tatjana N. , Bisschop Peter H. , Bravenboer Nathalie
Published: November 2018

Bone marrow adipose tissue (BMAT) increases after menopause, and increased BMAT is associated with osteoporosis and prevalent vertebral fractures. Peroxisome proliferator-activated receptor-γ (PPARγ) activation promotes adipogenesis and inhibits osteoblastogenesis; therefore, PPARγ is a potential contributor to the postmenopausal increase in BMAT and decrease in bone mass. The aim of this study is to determine if PPARγ inhibition can prevent ovariectomy-induced BMAT increase and bone loss in C3H/HeJ mice. Fourteen-week-old female C3H/HeJ mice ( n = 40) were allocated to four intervention groups: sham surgery (Sham) or ovariectomy (OVX; isoflurane anesthesia) with either vehicle (Veh) or PPARγ antagonist administration (GW9662; 1 mg·kg−1·day−1, daily intraperitoneal injections) for 3 wk. We measured BMAT volume, adipocyte size, adipocyte number. and bone structural parameters in the proximal metaphysis of the tibia using polyoxometalate-based contrast enhanced-nanocomputed topogaphy. Bone turnover was measured in the contralateral tibia using histomorphometry. The effects of surgery and treatment were analyzed by two-way ANOVA. OVX increased the BMAT volume fraction (Sham + Veh: 2.9 ± 2.7% vs. OVX + Veh: 8.1 ± 5.0%: P < 0.001), average adipocyte diameter (Sham + Veh: 19.3 ± 2.6 μm vs. OVX + Veh: 23.1 ± 3.4 μm: P = 0.001), and adipocyte number (Sham + Veh: 584 ± 337cells/μm3 vs. OVX + Veh: 824 ± 113cells/μm3: P = 0.03), while OVX decreased bone volume fraction (Sham + Veh: 15.5 ± 2.8% vs. OVX + Veh: 7.7 ± 1.9%; P < 0.001). GW9662 had no effect on BMAT, bone structural parameters, or bone turnover. In conclusion, ovariectomy increased BMAT and decreased bone volume in C3H/HeJ mice. The PPARγ antagonist GW9662 had no effect on BMAT or bone volume in C3H/HeJ mice, suggesting that BMAT accumulation is regulated independently of PPARγ in C3H/HeJ mice.
miR-1-3p Contributes to Cell Proliferation and Invasion by Targeting Glutaminase in Bladder Cancer Cells
Authors: Zhang Junfeng , Wang Longsheng , Mao Shiyu , Liu Mengnan , Zhang Wentao , Zhang Ziwei , Guo Yadong , Huang Bisheng , Yan Yang , Huang Yong , Yao Xudong 
Published: November 2018

Background/Aims: Increasing evidence showed that miR-1-3p plays a major role in malignant tumor progression. However, the specific biological function of miR-1-3p in bladder cancer is yet unknown. Methods: The expression levels of miR-1-3p in bladder cancer tissues and cell lines were examined by qRT-PCR. Bisulfite sequencing PCR was used for DNA methylation analysis. The target of miR-1-3p was validated by a dual luciferase reporter assay, and the effects of miR-1-3p on phenotypic changes in bladder cancer cells were investigated in vitro and in vivo. Results: The expression of miR-1-3p in bladder cancer cells was downregulated as compared to normal SV-HUC-1 cells. Also, the expression of miR-1-3p was significantly lower in bladder cancer tissues than the corresponding non-cancerous tissues. The methylation status of CpG islands was involved in the regulation of miR-1-3p expression. miR-1-3p inhibited the bladder cancer cell proliferation, migration, and invasion by directly targeting the 3’-UTR of glutaminase. It also exerted an anti-tumor effect by negatively regulating the glutaminase in a xenograft mouse model. Furthermore, GLS depletion resulted in the prolonged expression of γH2AX. Conclusion: Taken together, these results demonstrated that miR-1-3p acts as a tumor suppressor via regulation of glutaminase expression in bladder cancer progression, and miR-1-3p might represent a novel therapeutic target for the treatment of bladder cancer.
Sulforaphane-N-Acetyl-Cysteine Induces Autophagy Through Activation of ERK1/2 in U87MG and U373MG Cells
Authors: Liu Han-Jie , Wang Lei , Kang Lin , Du Juan , Li Sha , Cui Hui-Xian
Published: November 2018

Background/Aims: Sulforaphane-N-acetyl-cysteine (SFN-NAC) is a sulforaphane (SFN) metabolite with a longer half-life and better blood–brain barrier permeability than those of SFN. Previous studies have found that SFN-NAC can act via ERK to destroy microtubules and inhibit cell growth in lung cancer cells. However, the underlying mechanisms are unclear, and it is unknown whether SFN-NAC can inhibit the growth of glioma. Here, we have demonstrated for the first time that SFN-NAC activates autophagy-mediated downregulation of α-tubulin expression via the ERK pathway. Methods: U87MG and U373MG cells, two widely used glioma cell lines, were utilized in this study. Apoptosis assay, western blot analysis, co-immunoprecipitation, immunostaining, and electron microscopy were used to analyze the effect of SFN-NAC on α-tubulin and its interaction with microtube-associated protein 1 light-chain 3 (LC3). Results: SFN-NAC induced cell-cycle arrest in the G2/M phase and dose-dependently induced intracellular ERK activation, autophagy, and α-tubulin downregulation. These SFN-NAC-induced effects were reversed by inhibiting the ERK pathway with its inhibitor PD98059. U87MG and U373MG cells were transfected with LC3 small interfering RNA, and the subsequent inhibition of autophagy reversed the downregulation of α-tubulin by SFN-NAC. Furthermore, co-immunoprecipitation experiments and confocal microscopy confirmed that SFN-NAC promotes the binding of LC3 with α-tubulin in the cytoplasm. Cell viability experiments demonstrate that SFN-NAC inhibits the growth of U87MG and U373MG cell colonies. Conclusion: These findings suggest that SFN-NAC is a novel potential anti-glioma agent.
ВПЛИВ ГЛУТАТІОНУ НА БІОХІМІЧНІ ПОКАЗНИКИ СИРОВАТКИ КРОВІ ПРИ ЕКСПЕРИМЕНТАЛЬНІЙ НЕФРОПАТІЇ
Authors: Gerush I. V. , Grigorieva N. P. , Ferenchuk Ye. O.
Published: November 2018

Вступ.Захворювання нирок – одна з найпоширеніших та найактуальніших проблем сучасної медицини. В останні десятиліття активно вивчають нефропротекторні властивості різноманітних антиоксидантів з метою попередження та корекції порушень функцій нирок, однак дані щодо ролі різних антиоксидантів є фрагментарними і потребують подальших досліджень.

Мета дослідження– вивчити вплив глутатіону на зміну біохімічних показників крові за умов експериментальної нефропатії.

Методи дослідження. Досліди проводили на 90 білих статевозрілих щурах-самцях масою 0,16–0,18 кг. У двох серіях експериментів нефропатію викликали шляхом одноразового внутрішньочеревного введення фолієвої кислоти в дозах 200 та 250 мг/кг. Глутатіон вводили інтрагастрально в дозі 100 мг/кг упродовж трьох та семи днів. Для оцінки функціонального стану нирок проводили біохімічне дослідження крові з визначенням концентрації креатиніну, сечовини, альбуміну, загального білка, активності γ-глутамілтранс­пептидази та аланіламінотранспептидази.

Результати й обговорення.За умов нефропатії спостерігали збільшення вмісту сечовини порівняно з контрольною групою: на 27 % – на третій день експерименту, на 15 % – на сьомий. Введення глутатіону сприяло нормалізації досліджуваного показника. Було відзначено підвищення, порівняно з контрольною групою, рівня креатиніну в сироватці крові щурів із нефропатією в 1,5 раза при застосуванні фолієвої кислоти в дозі 200 мг/кг. На сьомий день експерименту він збільшився лише на 17 %. У групі тварин, в яких нефропатію викликали фолієвою кислотою в дозі 250 мг/кг, концентрація креатиніну підвищилась порівняно з контрольною групою: у 2,4 раза – на третій день експерименту, на 30 % – на сьомий. Семиденне введення глутатіону прирівнювало показники креатиніну піддослідних тварин до показників контрольної групи. Про загальну інтоксикацію організму під впливом високої концентрації фолієвої кислоти свідчили зниження білоксинтезувальної функції печінки, зростання активності γ-глутамілтранспептидази та аланіламінотранспептидази.

Висновки.Глутатіон проявляє нефропротекторні властивості, що підтверджується зниженням проявів нефротичного синдрому та поліпшенням функціональних показників нирок. Найбільш чутливий біохімічний показник за умов нефропатії – креатинін, вміст якого залежить від концентрації токсиканта, можна використовувати для діагностування стану нирок та підтвердження моделі нефропатії.
ACTION OF HYDROGEN SULFIDE DONORS ON NITROSO-OXIDATIVE PROCESSES IN SMALL INTESTINE OF RATS WITH METHOTREXATE-INDUCED ENTEROPATHY
Authors: Sklyarova Yu. O. , Fomenko I. S.
Published: November 2018

Introduction. Medication-induced enteropathy plays an important part among factors leading to the development of small intestinal injury. There are some evidences indicating a potential preventive action of hydrogen sulfide (H2S) donors against drug-induced enteropathies based on that fact that the use of the most of enterotoxic medications including anti-tumor drugs leads to the suppression of this gaseous mediator production.

The aim of the study – to compare the action of H2S donors in small intestine of rats on parameters of NO-synthase system and oxidative stress under condition of methotrexate-induced enteropathy.

Research Methods. The experimental procedures were carried out on rats which on the background of methotrexate-induced enteropathy received H2S donors NaHS (1 and 10 mg/kg) and L-cysteine. Following biochemical parameters were measured in small intestinal mucosa: activity of NO-synthases, myeloperoxidase, superoxide dismutase and catalase; concentrations of NOx (nitrite/nitrate) and malonic dialdehyde. H2S concentration was determined in blood serum.

Results and Discussion. Administration of methotrexate didn’t cause any visible changes of small intestine surface, however led to serious biochemical changes. NO concentration increased as a result of iNOS activation (more than fivefold (p≤0.01). Simultaneously concentration of H2S decreased in blood serum. Administration of H2.S donors practically returned these parameters to their normal value. Methotrexate-induced enteropathy caused the increase of myeloperoxidase activity by 66 %, p≤0.01, indicating of inflammatory process formation and activation of lipid peroxidation. Administration of NaHS didn’t cause any serious changes in myeloperoxidase activity, however increased SOD activity and practically retuned it to its norm.

Conclusions. Nirtoso-oxidative stress plays the key role in enteropathy formation resulted in methotrexate administration. H2S donors modulate parameters of NO-synthase system and activity of SOD.
ВМІСТ КИСЛОТ ГІДРОКСИКОРИЧНИХ У ТРАВІ ТА КОРЕНЕВИЩАХ І КОРЕНЯХ БЕДРИНЦЮ ЛОМИКАМЕНЕВОГО (PIMPINELLA SAXIFRAGA L.)
Authors: Parashchuk E. A. , Marchyshyn S. M. , Kyryliv M. V. , Bekus I. R.
Published: November 2018

Вступ. Бедринець ломикаменевий (Pimpinella saxifraga L.) з родини селерові (Apiaceae) здавна у народній медицині застосовують як відхаркувальний, сечогінний, протизапальний, седативний,  болетамувальний засіб. Його рекомендують при катарі дихальних шляхів, трахеїті, бронхіті, пневмонії, ларингіті, астмі, коклюші, водянці, сольових діатезах, захворюваннях печінки, атонії кишечника, хронічному гастриті зі зниженою кислотністю, подагрі, набряках та метеоризмі. З лікувальною метою використовують в основному кореневища і корені  рослини. Відомо близько 200 видів роду Бедринець (Pimpinella L.), поширених в Азії, Європі й Африці. В Україні зустрічаються 5 видів; найпоширенішим  є бедринець ломикаменевий.

 Мета дослідження – встановити наявність і визначити кількісний вміст кислот гідроксикоричних у траві та підземних органах бедринцю ломикаменевого.

Методи дослідження. Для виявлення кислот гідроксикоричних використовували спиртово-водну витяжку. Реакція з 1 % розчином ферум (ІІІ) хлориду (поява зелено-сірого забарвлення) свідчила про наявність у досліджуваній витяжці сполук фенольної природи. Кількісне визначення кислот гідроксикоричних у досліджуваних об’єктах ґрунтується на спектрофотометричному методі. Якісний склад і кількісний вміст індивідуальних кислот гідроксикоричних у траві та підземних органах бедринцю ломикаменевого досліджували методом високоефективної рідинної хроматографії на хроматографі Agilent 1200 3 D LC System Technologies (США).

Результати й обговорення. Кількісний вміст суми кислот гідроксикоричних у траві бедринцю ломикаменевого становив  (4,68±0,05) %, в підземних органах – (1,52±0,03) %. Методом високоефективної рідинної хроматографії в досліджуваних об’єктах рослини виявлено й ідентифіковано кислоти хлорогенову і розмаринову та встановлено їх кількісний вміст.  У траві й підземних органах бедринцю ломикаменевого в основному домінує кислота хлорогенова, вміст якої становив 3,13  і 0,11 % відповідно. У траві рослини міститься 0,34 % кислоти розмаринової.

Висновки. Встановлено наявність і визначено кількісний вміст кислот гідроксикоричних у траві та підземних органах бедринцю ломикаменевого, який становив (4,68±0,05) і (1,52±0,03) % відповідно. Методом високоефективної рідинної хроматографії в досліджуваній сировині  рослини виявлено індивідуальні кислоти гідроксикоричні – хлорогенову і  розмаринову, визначено їх кількісний вміст. У траві й підземних органах бедринцю ломикаменевого домінує кислота хлорогенова, вміст якої становив 3,13 і 0,34 % відповідно, тому її можна рекомендувати для стандартизації сировини.
ВПЛИВ ПРЕПАРАТУ L-АРГІНІНУ НА ЗМІНИ ПРОЦЕСІВ ПЕРОКСИДНОГО ОКИСНЕННЯ ЛІПІДІВ ТА АНТИОКСИДАНТНОЇ СИСТЕМИ В КРОВІ ЗА УМОВ КОМОРБІДНОЇ ПАТОЛОГІЇ – ІММОБІЛІЗАЦІЙНОГО СТРЕСУ ТА АДРЕНАЛІНОВОГО УШКОДЖЕННЯ МІОКАРДА
Authors: Lys O. B. , Regeda M. S.
Published: November 2018

Вступ. Активація адренергічної і гіпоталамо-гіпофізарно-адреналової систем призводить до виникнення стресорної тріади Сельє, першим компонентом якої є гіпертрофія надниркових залоз із збільшенням синтезу ними глюкокортикоїдів та катехоламінів. Аргінін слугує необхідним компонентом для синтезу білків і багатьох біологічно важливих молекул, таких, як орнітин, пролін, поліаміни, креатин і агматин. Однак головна його роль в організмі людини – бути субстратом для синтезу оксиду азоту.

Мета дослідження –вивчити вплив препарату L-аргініну на зміни процесів пероксидного окиснення ліпідів та антиоксидантної системи, що виникають у крові білих щурів під впливом гострого іммобілізаційного стресу й адреналіну.

Методи дослідження.Дослід проводили на білих щурах-самцях лінії Вістар масою 180–200 г, яких було поділено на три групи по 10 тварин у кожній (дві дослідні та одну контрольну).

Результати й обговорення. Встановлено, що за умов поєднаної патології (іммобілізаційного стресу й адреналінового ушкодження міокарда) до лікування L-аргініном активність у крові показників антиоксидантної системи – каталази і супероксиддисмутази зменшувалася на 5-ту добу експерименту. Було відзначено збільшення рівня продуктів пероксидного окиснення ліпідів – дієнових кон’югатів та малонового діальдегіду проти контролю. Використання L-аргініну протягом 5-ти днів призвело до підвищення активності каталази (на 107,2 %) і супероксиддисмутази (на 74,5 %) відносно групи тварин з поєднаною патологією в експерименті (іммобілізаційним стресом і адреналіновим ушкодженням міокарда) до лікування, що свідчить про антиоксидантний вплив даного препарату. Застосування L-аргініну протягом 5-ти днів знизило рівень дієнових кон’югатів (на 80,16 %, р<0,05) та малонового діальдегіду (на 42,26 %, р<0,05), що вказує на зменшення процесів пероксидного окиснення ліпідів.

Висновок.L-аргінін доцільно в подальшому і перспективно вивчати в експерименті та клініці з метою корекції метаболічних порушень за умов експериментального іммобілізаційного стресу й адреналінового ушкодження міокарда і розробки методичних рекомендацій.