bluuebunny/crossref_metadata_2025 huggingface dataset:
Landscape effects on pollination networks in Mediterranean gypsum islands
Authors: Santamaría S. , Sánchez A. M. , López‐Angulo J. , Ornosa C. , Mola I. , Escudero A.
Published: July 2017

Habitat fragmentation is a major driver of global change that has operated historically on Mediterranean ecosystems. However, more needs to be understood about how fragmentation influences ecological interactions, particularly pollination. Gypsum outcrops are historically fragmented Mediterranean habitats and settings for the evolution of many endangered soil‐specialist plants with narrow ranges.

In this study, we aimed to determine how fragmentation (area and connectivity) affects: (i) pollinator community composition and (ii) structural properties of pollination networks; and whether there are differences in the effects of fragmentation on: (iii) the number of interactions and visits among pollinator functional groups; and (iv) the number of interactions and specialisation degree between soil‐specialist and soil‐generalist plants. We characterised the degree of fragmentation and the pollination network structures in 12 gypsum habitat fragments embedded in a cropland matrix during two consecutive years.

We found significant relationships between fragmentation and network structure. The effects of fragmentation differed among pollinator functional groups, but not between soil‐specialist and soil‐generalist plants, in terms of number of interactions. However, the relatively higher pollinator specialisation of soil‐specialist plants suggested greater dependence on pollinators.

Inter‐annual variations in the network structures demonstrated the importance of temporal replication. The observed patterns related to the landscape structure and pollination at both the network and species levels provide insights into the key ecological processes in gypsum islands. These findings may help to identify the potential drivers of species persistence, especially for endangered soil‐specialist plants with narrow ranges in a changing scenario with exacerbated habitat fragmentation.
Activation of semantic information at the sublexical level during handwriting production: Evidence from inhibition effects of Chinese semantic radicals in the picture‐word interference paradigm
Authors: Chen Xuqian , Liao Yuanlan , Chen Xianzhe
Published: July 2017

Using a non‐alphabetic language (e.g., Chinese), the present study tested a novel view that semantic information at the sublexical level should be activated during handwriting production. Over 80% of Chinese characters are phonograms, in which semantic radicals represent category information (e.g., 椅 ‘chair,’ 桃 ‘peach,’ 橙 ‘orange’ are related to plants) while phonetic radicals represent phonetic information (e.g., 狼 ‘wolf,’ 朗 ‘brightness,’ 郎 ‘male,’ are all pronounced /lang/). Under different semantic category conditions at the lexical level (semantically related in Experiment 1; semantically unrelated in Experiment 2), the orthographic relatedness and semantic relatedness of semantic radicals in the picture name and its distractor were manipulated under different SOAs (i.e., stimulus onset asynchrony, the interval between the onset of the picture and the onset of the interference word). Two questions were addressed: (1) Is it possible that semantic information could be activated in the sublexical level conditions? (2) How are semantic and orthographic information dynamically accessed in word production? Results showed that both orthographic and semantic information were activated under the present picture‐word interference paradigm, dynamically under different SOAs, which supported our view that discussions on semantic processes in the writing modality should be extended to the sublexical level. The current findings provide possibility for building new orthography‐phonology‐semantics models in writing.
Threshold Estimation for Stochastic Processes with Small Noise
Authors: Shimizu Yasutaka
Published: July 2017

Consider a process satisfying a stochastic differential equation with unknown drift parameter, and suppose that discrete observations are given. It is known that a simple least squares estimator (LSE) can be consistent but numerically unstable in the sense of large standard deviations under finite samples when the noise process has jumps. We propose a filter to cut large shocks from data and construct the same LSE from data selected by the filter. The proposed estimator can be asymptotically equivalent to the usual LSE, whose asymptotic distribution strongly depends on the noise process. However, in numerical study, it looked asymptotically normal in an example where filter was chosen suitably, and the noise was a Lévy process. We will try to justify this phenomenon mathematically, under certain restricted assumptions.
The best teacher is like a famous mage everyone knows – Just not any of your favorites
Authors: Paffenroth Kim
Published: July 2017

This essay draws out the useful parallels between the best kind of teacher and the Good Witch of the North, Glinda, from The Wizard of Oz. Unappealing to many viewers or readers of the classic children's story, Glinda offers an inspiring reminder of four important pedagogical points: (1) the master teacher always treats her student as a peer; (2) the master teacher acknowledges and encourages her student's abilities but lets her learn how to exercise them on her own; (3) the master teacher is often not equivalent or even similar to anyone the student has encountered before; and (4) the master teacher is not a surrogate parent but a more distant figure.
Reduction of Zika virus infectivity in platelet concentrates after treatment with ultraviolet C light and in plasma after treatment with methylene blue and visible light
Authors: Fryk Jesse J. , Marks Denese C. , Hobson‐Peters Jody , Watterson Daniel , Hall Roy A. , Young Paul R. , Reichenberg Stefan , Tolksdorf Frank , Sumian Chryslain , Gravemann Ute , Seltsam Axel , Faddy Helen M.
Published: July 2017

BACKGROUND

Zika virus (ZIKV) has emerged as a potential threat to transfusion safety worldwide. Pathogen inactivation is one approach to manage this risk. In this study, the efficacy of the THERAFLEX UV‐Platelets system and THERAFLEX MB‐Plasma system to inactivate ZIKV in platelet concentrates (PCs) and plasma was investigated.

STUDY DESIGN AND METHODS

PCs spiked with ZIKV were treated with the THERAFLEX UV‐Platelets system at 0.05, 0.10, 0.15, and 0.20 J/cm2 UVC. Plasma spiked with ZIKV was treated with the THERAFLEX MB‐Plasma system at 20, 40, 60, and 120 J/cm2 light at 630 nm with at least 0.8 µmol/L methylene blue (MB). Samples were taken before the first and after each illumination dose and tested for residual virus. For each system the level of viral reduction was determined.

RESULTS

Treatment of PCs with THERAFLEX UV‐Platelets system resulted in a mean of 5 log reduction in ZIKV infectivity at the standard UVC dose (0.20 J/cm2), with dose dependency observed with increasing UVC dose. For plasma treated with MB and visible light, ZIKV infectivity was reduced by a mean of at least 5.68 log, with residual viral infectivity reaching the detection limit of the assay at 40 J/cm2 (one‐third the standard dose).

CONCLUSIONS

Our study demonstrates that the THERAFLEX UV‐Platelets system and THERAFLEX MB‐Plasma system can reduce ZIKV infectivity in PCs and pooled plasma to the detection limit of the assays used. These findings suggest both systems have the capacity to be an effective option to manage potential ZIKV transfusion transmission risk.
Mitochondrial proteostasis as a shared characteristic of slowed aging: the importance of considering cell proliferation
Authors: Hamilton Karyn L. , Miller Benjamin F.
Published: July 2017

Proteostasis is one of the seven “pillars of aging research” identified by the Trans‐NIH Geroscience Initiative and loss of proteostasis is associated with aging and age‐related chronic disease. Accumulated protein damage and resultant cellular dysfunction are consequences of limited protein repair systems and slowed protein turnover. When relatively high rates of protein turnover are maintained despite advancing age, damaged proteins are more quickly degraded and replaced, maintaining proteome fidelity. Therefore, maintenance of protein turnover represents an important proteostatic mechanism. However, measurement of protein synthesis without consideration for cell proliferation can result in an incomplete picture, devoid of information about how new proteins are being allocated. Simultaneous measurement of protein and DNA synthesis provides necessary mechanistic insight about proteins apportioned for newly proliferating cells versus for somatic maintenance. Using this approach with a number of murine models of slowed aging shows that, compared to controls, energetic resources are directed more toward somatic maintenance and proteostasis, and away from cell growth and proliferation. In particular, slowed aging models are associated with heightened mechanisms of mitochondrial proteostatic maintenance. Taking cell proliferation into account may explain the paradoxical findings that aging itself and slowed aging interventions can both be characterized by slower rates of protein synthesis.

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Zeeman effect experiment with high-resolution spectroscopy for advanced physics laboratory
Authors: Taylor Andrew S. , Hyde Alexander R. , Batishchev Oleg V.
Published: July 2017

An experiment studying the physics underlying the Zeeman effect and the Paschen-Back effect is developed for an advanced physics laboratory. We have improved upon the standard Zeeman effect experiment by eliminating the Fabry-Perot etalon, so that virtually any emission line in the visible spectrum can be analyzed. The magnetic field is provided by neodymium magnets. Light emitted in the ∼1 T field is analyzed by a Czerny-Turner spectrograph equipped with medium-dispersion grating and small-pixel imaging CCD. A spectral resolution under 1 pm/pixel is achieved. The splitting of argon and helium lines is measured as a function of field strength. The proportionality of the splitting magnitude to the B-field strength and to λ2 is demonstrated. The Bohr magneton is calculated and compared to the theoretical value.
STING is an essential mediator of the Ku70-mediated production of IFN-λ1 in response to exogenous DNA
Authors: Sui Hongyan , Zhou Ming , Imamichi Hiromi , Jiao Xiaoli , Sherman Brad T. , Lane H. Clifford , Imamichi Tomozumi
Published: July 2017

The adaptor protein STING mediates the production of type III interferon in response to cytosolic DNA and DNA viruses.
Paper of note in
Science Translational Medicine
9
(398)
Authors: Ferrarelli Leslie K.
Published: July 2017

This week’s article describes an epigenetic target for treating kidney cancer.
Papers of note in
Nature
547
(7662)
Authors: VanHook Annalisa M.
Published: July 2017

This week’s articles describe mechanisms that control the proliferation of cardiac cells during injury repair, personalized vaccines for treating cancer, and a mechanism by which malaria parasites sense host nutrients.
The Norepinephrine Metabolite 3,4-Dihydroxymandelic Acid Is Produced by the Commensal Microbiota and Promotes Chemotaxis and Virulence Gene Expression in Enterohemorrhagic Escherichia coli
Authors: Sule Nitesh , Pasupuleti Sasi , Kohli Nandita , Menon Rani , Dangott Lawrence J. , Manson Michael D. , Jayaraman Arul
Published: July 2017

Enterohemorrhagic
Escherichia coli
(EHEC) is a commonly occurring foodborne pathogen responsible for numerous multistate outbreaks in the United States. It is known to infect the host gastrointestinal tract, specifically, in locations associated with lymphoid tissue. These niches serve as sources of enteric neurotransmitters, such as epinephrine and norepinephrine, that are known to increase virulence in several pathogens, including enterohemorrhagic
E. coli
. The mechanisms that allow pathogens to target these niches are poorly understood. We previously reported that 3,4-dihydroxymandelic acid (DHMA), a metabolite of norepinephrine produced by
E. coli
, is a chemoattractant for the nonpathogenic
E. coli
RP437 strain. Here we report that DHMA is also a chemoattractant for EHEC. In addition, DHMA induces the expression of EHEC virulence genes and increases attachment to intestinal epithelial cells
in vitro
in a QseC-dependent manner. We also show that DHMA is present in murine gut fecal contents and that its production requires the presence of the commensal microbiota. On the basis of its ability to both attract and induce virulence gene expression in EHEC, we propose that DHMA acts as a molecular beacon to target pathogens to their preferred sites of infection
in vivo
.
Rifaximin versus norfloxacin for prevention of spontaneous bacterial peritonitis: a systematic review
Authors: Sidhu Gurpartap S , Go Andrew , Attar Bashar M , Mutneja Hemant R , Arora Shilpa , Patel Sanjay A
Published: July 2017

Aim

The aim of this systematic review is to evaluate the efficacy and safety of rifaximin in the prophylaxis of spontaneous bacterial peritonitis (SBP) as compared with norfloxacin.

Methods

We searched MEDLINE, CINAHL, Google Scholar and Cochrane databases from inception to January 2017. Reference lists of articles as well as conference proceedings were manually screened. We included studies that recruited patients with cirrhosis and ascites who met the criteria for primary or secondary SBP prophylaxis as defined by the European Association for the Study of the Liver and American Association for the Study of Liver Diseases. Two independent investigators reviewed the studies for eligibility, extracted the data and assessed study quality using the Cochrane risk of bias tool. The primary outcome was occurrence of SBP. Secondary outcomes included mortality and adverse events with therapy.

Results

Of the 435 studies identified, a total of five were included for full-text review. Four studies were eligible for the systematic review, three of which were randomised controlled trials and one was a prospective observational study. The population examined in majority of studies was primarily hepatitis C cirrhosis. The results of individual studies indicated either superior efficacy of rifaximin or no statistical difference between rifaximin and norfloxacin for SBP prophylaxis.

Conclusions

Moderate-quality evidence shows that long-term use of rifaximin appears to be a reasonable alternative to norfloxacin for SBP prevention in hepatitis C cirrhosis.
Fine-scale habitat selection of green sturgeon (Acipenser medirostris) within three spawning locations in the Sacramento River, California
Authors: Wyman M.T. , Thomas M.J. , McDonald R.R. , Hearn A.R. , Battleson R.D. , Chapman E.D. , Kinzel P. , Minear J.T. , Mora E.A. , Nelson J.M. , Pagel M.D. , Klimley A.P.
Published: July 2017

Vast sections of the Sacramento River have been listed as critical habitat by the National Marine Fisheries Service for green sturgeon spawning (Acipenser medirostris), yet spawning is known to occur at only a few specific locations. This study reveals the range of physical habitat variables selected by adult green sturgeon during their spawning period. We integrated fine-scale fish positions, physical habitat characteristics, discharge, bathymetry, and simulated velocity and depth using a two-dimensional hydraulic model (FaSTMECH). The objective was to create habitat suitability curves for depth, velocity, and substrate type within three known spawning locations over two years. An overall cumulative habitat suitability score was calculated that averaged the depth, velocity, and substrate scores over all fish, sites, and years. A weighted usable area index was calculated throughout the sampling periods for each of the three sites. Cumulative results indicate that the microhabitat characteristics most preferred by green sturgeon in these three spawning locations were velocities between 1.0 and 1.1 m/s, depths of 8–9 m, and gravel and sand substrate. This study provides guidance for those who may in the future want to increase spawning habitat for green sturgeon within the Sacramento River.
Electronic cigarettes—A review of the physiological health effects
Authors: Zucchet Alyssa , Schmaltz Grégory
Published: July 2017

Electronic cigarettes (ECs) are devices that are used recreationally or as smoking cessation tools, and have become increasingly popular in recent years. We conducted a review of the available literature to determine the health effects caused by the use of these devices. A heating element in the EC aerosolizes a solution of propylene glycol, glycerol, nicotine (optional), and flavouring (optional). These compounds are generally harmless on their own. However, upon heating, they produce various carcinogens and irritants. We found that concentrations of these toxicants vary significantly depending on the type of EC device, the type of EC liquid, and the smoking behaviour of the user. Exposure to these vapours can cause inflammation and oxidative damage to in vitro and in vivo cells. EC aerosol can also potentially affect organ systems and especially cardiovascular and lung function. We concluded that EC use causes acute effects on health but not as severe as those of conventional cigarettes (CCs). These devices could, therefore, be of use for smokers of CCs wishing to quit. However, as EC aerosol introduces new toxicants not found in CCs, long-term studies are needed to investigate possible chronic effects associated with EC use.
INNOVATIONS IN THE SUSTAINABLE MANAGEMENT OF LOCAL GOVERNMENT LIABILITIES IN CHINA
Authors: SHI JINCHUAN , WANG ZHIKAI , WANG XIAOJIANG
Published: July 2017

Through the first and second year of China’s 13th five-year plan coincided with local governments holding their own “Two Sessions” before attending the “Two Congresses” in Beijing in March. As one of the frequent results, the issue of local government debt naturally became a popular topic. The scale of local government debt in China was/is considerable, and the structure is complex, which poses a threat to sustained economic development. To address this situation, China must regulate local government debt, clean up urban financing vehicle debt, foster and manage the local bond market, and introduce innovation in the management of local government liability. Only through initiatives such as this will China gain control of local government debt and thus support and promote the long-term sustainable growth of the economy.
Tunable properties of one-dimensional photonic crystals that incorporate a defect layer of a magnetized plasma
Authors: Aly Arafa H. , Elsayed Hussein A. , Ameen Ayman A. , Mohamed S. H.
Published: July 2017

In this paper, we theoretically investigate the transmittance characteristics of one-dimensional defective photonic crystal in microwave radiations based on the fundamentals of the characteristic matrix method. Here, the defect layer is magnetized plasma. The numerical results show the appearance of defect peaks inside the Photonic Band Gap. The external magnetic field has a significant effect on the permittivity of the defect layer. Therefore, the position and intensity of the defect peak are strongly affected by the external magnetic field. Moreover, we have investigated the different parameters on the defect peaks as the plasma density, the thickness of the plasma layer and the angle of incidence. Wherefore, the proposed structure could be the cornerstone for many applications in microwave regions such as narrowband filters.
Ribosomal Stalling During Translation: Providing Substrates for Ribosome-Associated Protein Quality Control
Authors: Joazeiro Claudio A.P.
Published: July 2017

Cells of all organisms survey problems during translation elongation, which may happen as a consequence of mRNA aberrations, inefficient decoding, or other sources. In eukaryotes, ribosome-associated quality control (RQC) senses elongation-stalled ribosomes and promotes dissociation of ribosomal subunits. This so-called ribosomal rescue releases the mRNA for degradation and allows 40S subunits to be recycled for new rounds of translation. However, the nascent polypeptide chains remain linked to tRNA and associated with the rescued 60S subunits. As a final critical step in this pathway, the Ltn1/Listerin E3 ligase subunit of the RQC complex (RQCc) ubiquitylates the nascent chain, which promotes clearance of the 60S subunit while simultaneously marking the nascent chain for elimination. Here we review the ribosomal stalling and rescue steps upstream of the RQCc, where one witnesses intersection with cellular machineries implicated in translation elongation, translation termination, ribosomal subunit recycling, and mRNA quality control. We emphasize both recent progress and future directions in this area, as well as examples linking ribosomal rescue with the production of Ltn1-RQCc substrates.
Science, Technology, Society, and Law
Authors: Cole Simon A. , Bertenthal Alyse
Published: July 2017

Law and regulation increasingly interact with science, technology, and medicine in contemporary society. Law and social science (LSS) analyses can therefore benefit from rigorous, nuanced social scientific accounts of the nature of scientific knowledge and practice. Over the past two decades, LSS scholars have increasingly turned for such accounts to the field known as science and technology studies (STS). This article reviews the LSS literature that draws on STS. Our discussion is divided into two primary sections. We first discuss LSS literature that draws on STS because it deals with issues in which law and science interact. We then discuss literature that draws on STS because it sees law as analogous to science as a knowledge-producing institution amenable to social science analysis. We suggest that through both of these avenues STS can encourage a newly critical view within LSS scholarship.
Single-Subject Studies in Translational Nutrition Research
Authors: Schork Nicholas J. , Goetz Laura H.
Published: July 2017

There is a great deal of interest in personalized, individualized, or precision interventions for disease and health-risk mitigation. This is as true of nutrition-based intervention and prevention strategies as it is for pharmacotherapies and pharmaceutical-oriented prevention strategies. Essentially, technological breakthroughs have enabled researchers to probe an individual's unique genetic, biochemical, physiological, behavioral, and exposure profile, allowing them to identify very specific and often nuanced factors that an individual might possess, which may make it more or less likely that he or she responds favorably to a particular intervention (e.g., nutrient supplementation) or disease prevention strategy (e.g., specific diet). However, as compelling and intuitive as personalized nutrition might be in the current era in which data-intensive biomedical characterization of individuals is possible, appropriately and objectively vetting personalized nutrition strategies is not trivial and requires novel study designs and data analytical methods. These designs and methods must consider a very integrated use of the multiple contemporary biomedical assays and technologies that motivate them, which adds to their complexity. Single-subject or N-of-1 trials can be used to assess the utility of personalized interventions and, in addition, can be crafted in such a way as to accommodate the necessarily integrated use of many emerging biomedical technologies and assays. In this review, we consider the motivation, design, and implementation of N-of-1 trials in translational nutrition research that are meant to assess the utility of personalized nutritional strategies. We provide a number of example studies, discuss appropriate analytical methods given the complex data they generate and require, and consider how such studies could leverage integration of various biomarker assays and clinical end points. Importantly, we also consider the development of strategies and algorithms for matching nutritional needs to individual biomedical profiles and the issues surrounding them. Finally, we discuss the limitations of personalized nutrition studies, possible extensions of N-of-1 nutritional intervention studies, and areas of future research.
The Transduction Cascade in Retinal ON-Bipolar Cells: Signal Processing and Disease
Authors: Martemyanov Kirill A. , Sampath Alapakkam P.
Published: July 2017

Our robust visual experience is based on the reliable transfer of information from our photoreceptor cells, the rods and cones, to higher brain centers. At the very first synapse of the visual system, information is split into two separate pathways, ON and OFF, which encode increments and decrements in light intensity, respectively. The importance of this segregation is borne out in the fact that receptive fields in higher visual centers maintain a separation between ON and OFF regions. In the past decade, the molecular mechanisms underlying the generation of ON signals have been identified, which are unique in their use of a G-protein signaling cascade. In this review, we consider advances in our understanding of G-protein signaling in ON-bipolar cell (BC) dendrites and how insights about signaling have emerged from visual deficits, mostly night blindness. Studies of G-protein signaling in ON-BCs reveal an intricate mechanism that permits the regulation of visual sensitivity over a wide dynamic range.
Empirical Comparison of Visualization Tools for Larger-Scale Network Analysis
Authors: Pavlopoulos Georgios A. , Paez-Espino David , Kyrpides Nikos C. , Iliopoulos Ioannis
Published: July 2017

Gene expression, signal transduction, protein/chemical interactions, biomedical literature cooccurrences, and other concepts are often captured in biological network representations where nodes represent a certain bioentity and edges the connections between them. While many tools to manipulate, visualize, and interactively explore such networks already exist, only few of them can scale up and follow today’s indisputable information growth. In this review, we shortly list a catalog of available network visualization tools and, from a user-experience point of view, we identify four candidate tools suitable for larger-scale network analysis, visualization, and exploration. We comment on their strengths and their weaknesses and empirically discuss their scalability, user friendliness, and postvisualization capabilities.
A Developed Optimization Method of Tight Reservoir Porosity
Authors: Wu Fenqiang , Xu Jingling
Published: July 2017

The optimization method to evaluate the tight reservoir porosity is a difficult technique to use due to its complexity and instability. This paper proposes an improved optimization method to calculate the porosity of tight reservoirs. First, we applied the matrix model which modified the multicomponent model to the problem and it improved the results by deducing a mathematical model. Second, we used the Simulated Annealing Algorithm to calculate the incoherence function, and then based on statistical theory, we obtained the most optimal results. Examples show that the method is effective, and despite the lack of the local experience parameters, its application is valuable in order to evaluate the porosity.
Study on the Damping of the Discontinuous Deformation Analysis Based on Two‐Block Model
Authors: Feng Xixia , Jiang Qinghui , Wu Aiqing , Wei Wei , Zhang Xiaobo
Published: July 2017

The deformation and failure of rock mass is a process of energy dissipation; the damping of DDA is a very important and basic problem. The correctness and effectiveness of DDA rely on the appropriate values of the numeric controlling parameters like time interval, spring stiffness, and assumed maximum displacement ratio g2, and the contact using the penalty method is the core content of DDA. A mechanical model of two contact blocks loaded with the normal force acting along one side of block boundary is established to study the DDA damping problem, which involves the contact and eliminates the influence of some numeric control parameters (e.g., g2). Based on the Newmark method and the theory of DDA, the motion equations of two‐block system can be established, and then the relationship of some numeric control parameters and the influence of damping can be obtained. The algorithmic damping increases with the increasing of time interval. Given a very small time interval, the spring stiffness may have no obvious effect on the algorithmic damping. The numerical results reveal that the essence of time interval influencing the open‐close iteration is the fact that the algorithmic damping is mainly controlled by time interval.
MCPIP1 Downregulation in Clear Cell Renal Cell Carcinoma Promotes Vascularization and Metastatic Progression
Authors: Marona Paulina , Górka Judyta , Mazurek Zofia , Wilk Waclaw , Rys Janusz , Majka Marcin , Jura Jolanta , Miekus Katarzyna
Published: July 2017

Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer and it forms highly vascularized tumors. The monocyte endoribonuclease MCPIP1 negatively regulates inflammation by degrading mRNA encoding proinflammatory cytokines, such as IL6, IL1, and IL12. MCPIP1 is also a negative regulator of NFκB and AP1 activity and it influences a broad range of miRNA activities. Here we report that MCPIP1 protein levels are decreased during renal cancer progression. In patient-derived tumors and xenografts established in NOD-SCID or nude mice, low MCPIP1 levels correlated strongly with increased proliferation, tumor outgrowth, and vascularity. MCPIP1 activity regulated secretion of VEGF, IL8, and CXCL12 leading to chemotaxis of microvascular endothelial cells, phosphorylation of VE-cadherin, and increased vascular permeability. Mechanistic investigations showed that MCPIP1 regulated ccRCC cell motility, lung metastasis, and mesenchymal phenotype by regulating key elements in the EMT signaling axis. Overall, our results illuminate how MCPIP1 serves as a key nodal point in coordinating tumor growth, angiogenesis, and metastatic spread in ccRCC. Cancer Res; 77(18); 4905–20. ©2017 AACR.
PI3Kγ/δ and NOTCH1 Cross-Regulate Pathways That Define the T-cell Acute Lymphoblastic Leukemia Disease Signature
Authors: Efimenko Evgeni , Davé Utpal P. , Lebedeva Irina V. , Shen Yao , Sanchez-Quintero Maria J. , Diolaiti Daniel , Kung Andrew , Lannutti Brian J. , Chen Jianchung , Realubit Ronald , Niatsetskaya Zoya , Ten Vadim , Karan Charles , Chen Xi , Califano Andrea , Diacovo Thomas G.
Published: July 2017

PI3K/AKT and NOTCH1 signaling pathways are frequently dysregulated in T-cell acute lymphoblastic leukemias (T-ALL). Although we have shown that the combined activities of the class I PI3K isoforms p110γ and p110δ play a major role in the development and progression of PTEN-null T-ALL, it has yet to be determined whether their contribution to leukemogenic programing is unique from that associated with NOTCH1 activation. Using an Lmo2-driven mouse model of T-ALL in which both the PI3K/AKT and NOTCH1 pathways are aberrantly upregulated, we now demonstrate that the combined activities of PI3Kγ/δ have both overlapping and distinct roles from NOTCH1 in generating T-ALL disease signature and in promoting tumor cell growth. Treatment of diseased animals with either a dual PI3Kγ/δ or a γ-secretase inhibitor reduced tumor burden, prolonged survival, and induced proapoptotic pathways. Consistent with their similar biological effects, both inhibitors downregulated genes involved in cMYC-dependent metabolism in gene set enrichment analyses. Furthermore, overexpression of cMYC in mice or T-ALL cell lines conferred resistance to both inhibitors, suggesting a point of pathway convergence. Of note, interrogation of transcriptional regulators and analysis of mitochondrial function showed that PI3Kγ/δ activity played a greater role in supporting the disease signature and critical bioenergetic pathways. Results provide insight into the interrelationship between T-ALL oncogenic networks and the therapeutic efficacy of dual PI3Kγ/δ inhibition in the context of NOTCH1 and cMYC signaling. Mol Cancer Ther; 16(10); 2069–82. ©2017 AACR.
Pilot Study of a “Large-Eye,” Surgically Induced Dry Eye Rabbit Model by Selective Removal of the Harderian, Lacrimal, and Meibomian Glands
Authors: Polans Arthur S. , McAnulty Jonathan F. , Phelps Paul O. , Darjatmoko Soesiawati R. , Burris Christopher K. , Albert Daniel M.
Published: July 2017

Background/Aims: Establish a reliable rabbit dry eye (DE) model. Methods: An interventional cohort study surgically removing glands contributing to the tear film. Eight rabbits were studied after removal of left lacrimal, Harderian, or both glands. Additional rabbits had Meibomian glands in the left eye thermally obstructed. All were followed for 10 weeks with phenol red thread (PRT) and slit-lamp examination with 2% fluorescein. We assessed corneal sensitivity using a Cochet-Bonnet esthesiometer. Outcome measures were severity/duration of reduced PRT, punctate epithelial erosions (PEE), and histologic evidence of corneal pannus. Results: Fluorescein staining demonstrated signs of dryness including PEE in all of the interventional eyes. The subjective measurement of epithelial erosions correlated with decreased tear production. PRT measurements in the control eyes averaged 31.54 mm (±1.83) and 22.71 mm (±1.60) in the eight left eyes, without loss of corneal sensitivity. Conclusions: Surgical removal of either the Harderian or lacrimal gland results in statistically significant decreases in tear volume and the development of severe DE. Removal of both glands results in the occurrence of a DE of comparable severity/duration to removal of either the lacrimal or Harderian gland alone. Meibomian gland obstruction contributes less to the DE model.
Karyotype Evolution and Phylogenetic Relationships of Cricetulus sokolovi Orlov et Malygin 1988 (Cricetidae, Rodentia) Inferred from Chromosomal Painting and Molecular Data
Authors: Poplavskaya Natalia S. , Romanenko Svetlana A. , Serdyukova Natalia A. , Trifonov Vladimir A. , Yang Fengtang , Nie Wenhui , Wang Jinghuan , Bannikova Anna A. , Surov Alexey V. , Lebedev Vladimir S.
Published: July 2017

Sokolov's dwarf hamster (Cricetulus sokolovi) is the least studied representative of the striped hamsters (Cricetulus barabensis species group), the taxonomy of which remains controversial. The species was described based on chromosome morphology, but neither the details of the karyotype nor the phylogenetic relationships with other Cricetulus are known. In the present study, the karyotype of C. sokolovi was examined using cross-species chromosome painting. Molecular and cytogenetic data were employed to determine the phylogenetic position of Sokolov's hamster and to analyze the potential pathways of chromosome evolution in Cricetulus. Both the chromosome and molecular data support the species status of Sokolov's hamster. Phylogenetic analysis of the CYTB data placed C. sokolovi as sister to all other striped hamsters (sequence divergence of 8.1%). FISH data revealed that the karyotype of C. sokolovi is highly rearranged, with the most parsimonious scenario of its origin implying at least 4 robertsonian events and a centromere shift. Comparative cytogenetic data on Cricetinae suggest that their evolutionary history includes both periods of chromosomal conservatism and episodes of rapid chromosomal change.
Serum Hyaluronic Acid Levels Are Altered in Acute Leukemia Patients: Potential Prognostic Implications
Authors: Anagnostopoulou Eleni , Papanastasopoulou Chrysanthi , Papastamataki Maria , Kotsiou Antonia , Topouzoglou Zoi , Anagnostopoulos Nikolaos , Sitaras Nikolaos
Published: July 2017

Background: Studies on the serum concentration of hyaluronic acid (HA) in newly diagnosed patients with acute myeloid leukemia (AML), B-acute lymphoblastic leukemia (B-ALL), and mantle-cell lymphoma (MCL) are scarce. In this study, we focused on investigating whether HA could serve as a possible prognostic marker in patients with AML, B-ALL, and MCL. Methods: The serum concentration of HA was measured in a total of 51 patients with newly diagnosed AML, B-ALL, and MCL. Venous blood was collected 1 day before the initiation of chemotherapy (D0), on day 16 of the first cycle of chemotherapy (D16), and on D30. Results: The serum HA concentration on D0 in patients with AML, B-ALL, and MCL was higher than in the control group. For all types of hematological malignancy, on D0, serum HA values of nonsurvivors were higher than in survivors. Moreover, patients in relapse had higher levels of serum HA than patients in remission. A strong positive correlation between serum HA and ferritin, β2-microglobulin, and lactate dehydrogenase was found. Conclusion: Serum HA may serve as a possible prognostic marker for AML, B-ALL, and MCL patients, especially on D0. Prospective case-control studies on larger populations may provide further information.
Дослідження деяких показників клітинного імунітету у хворих на розповсюджений псоріаз
Authors: Zagayko A. L. , Galuzinska L. V.
Published: July 2017

Introduction. Immune disorders play an important role in the pathogenesis of psoriasis. So, despite the fact that the data of immunological studies are very numerous, they are sometimes contradictory and not comparable, which is probably connected with the use of different methodological approaches, without taking into account clinical features of the disease, stage of the process, accompanied by a pathology.The aim of the work – to investigate some parameters of cellular immunity in patients with common psoriasis.Methods of the research. The following indices: content of T-lymphocytes (CD 3+) T-lymphocytes helper cells (CD4), T cytotoxic cells (CD8), B lymphocytes (CD 19), the factor of apoptosis FASx, endotheline-1 were measured.Results and Discussion. Analysis of cellular immunity in patients with psoriasis indicates an increase, when compared with healthy patients, T-lymphocytes (BG3+) T-lymphocytes helper cells (CD4), T cytotoxic cells (CD8), with progressive and inpatient stages of the disease. It was found that patients in the progressive stage of cell death significantly increased. In patients with progressive stage of psoriasis revealed an increased content of polypeptide–endothelin that indicates, on the one hand, the violation of vascular endothelium in psoriasis, and on the other, rate of tissue differentiation and apoptosis.Conclusions. The data obtained indicate significant changes of parameters of cellular immunity in patients with advanced stage.
Дослідження впливу екстрактів з листя стевії та чорниці на показники розвитку експериментального цукрового діабету, індукованого високофруктозною дієтою з додаванням ін’єкцій дексаметазону
Authors: Zagayko A. L. , Chumak O. I.
Published: July 2017

Introduction. Diabetes mellitus type 2 (DM 2) is a metabolic disease, which is characterized by chronic hyperglycemia. It develops as a result of insulin secretion disorder or mechanisms of its interaction with tissue cells. It is known that hyperglycemia is the main cause of cardiovascular complications development.The aim of the work – to study the effect of dry extracts from stevia and bilberry leaves on the metabolic disorders development in rats with experimental diabetes mellitus, caused by dexamethozone on a high-fructose diet ground.Methods of the research. The concentration of glycosylated hemoglobin, the level of fructosamine, the area under the glycemic curves, the level of immunoreactive insulin have been determined in the serum. Lipoperoxidation indicators have been determined according to diene conjugates (DC) and TBA-reactive products (TBA-RAP) content, the state of the antioxidant system has been assessed by reduced glutathione concentration determining (GSH) [8]. The significance of intergroup differences have been assessed due to Student's t-criterion.Results and discussion The introduction of low-dose dexamethasone in laboratory animals causes a complex of disorders, which are specific for metabolic syndrome and type 2 diabetes. Thus, a rise in the level of glycosylated hemoglobin, a concentration of fructosamine, a glucose level, a basal glycemia level, an increase in the area under the glycemic curves are observed in the serum of rats under the indicated conditions. With the introduction of dry extracts of stevia and bilberry leaves together with dexamethasone, the normalizing influence of these substances on the investigated indicators is observed.Conclusions. The use of dry extracts from stevia and bilberry leaves has a normalizing effect on glycosylation indicators, glucose level and lipid metabolism in the rats’ serum in type 2 diabetes mellitus. The more pronounced antioxidant effect of the extract from bilberry leaves and the hypoglycemic action of the extract from stevia leaves have been shown. This proves the advisability of the extracts from stevia and bilberry leaves joint application with the aim of drugs creation on their basis for metabolic disorders correction.
Застосування ентеросорбенту “карболайн” для корекції окиснювальних процесів у щурів різного віку, уражених натрію нітритом на тлі тютюнової інтоксикації
Authors: Lykhatskyi P. H. , Fira L. S.
Published: July 2017

Introduction. One of the priorities of toxicology and medicine is the study of the characteristics and mechanisms of action of combined xenobiotics – many risk factors for environmentally dependent diseases. Under the influence of extreme factors of various origins (heavy metals, nitrates, pesticides, tobacco, alcohol), formation of ROS, leading to the development of oxidative stress in the organism, which is accompanied by activation of lipid peroxidation and oxidative modification of proteins is enhanced. Under these conditions antioxidants and sorbents are commonly used.The aim of the study – to explore efficiency of enterosorbent karbolayn and its effect on oxidative processes in rats of different ages affected by sodium nitrite on the background of the 30-day tobacco intoxication.Research Methods. Given the defeat of rats of different ages sodium nitrite on the background of tobacco intoxication were tested for the ROS in the population of neutrophils, obtained by centrifugation on a double density gradient 1.077 and 1.093 ficoll-verografin, the content of TBA-active products in reaction with thiobarbituric acid and oxidative modification of proteins 2.4 dynitrofenilhidrazones content.Results and Discussion. The highest activity of free radical processes was marked after the defeat of sodium nitrite in 72 hours to 30 day of suspension toxicity of tobacco smoke. Immature and old rats were much more sensitive to the action of toxins than mature animals. Immature and old rats were much more sensitive to the action of toxins than mature animals. In order to inhibition of oxidative processes activated sorbent used by us karbolayn led to a slight normalization of the studied parameters. There was a trend toward reduction of reactive oxygen species in blood, TBA-active products and 2.4 dynitrophenilhidrazones in the studied tissues.Conclusions. The results indicate the advisability of including karbolayn to comprehensive treatment of poisoning of various origins.
Аналіз потенціалу системи глутатіону у щурів з аліментарним ожирінням
Authors: Marushchak M. I. , Mialiuk O. P. , Hevko U. P. , Habor H. H. , Yaroshenko T. Ya. , Antonyshyn I. V.
Published: July 2017

Introduction. Molecular mechanisms of urgent and long-term adaptation to the pathological process are realized with the participation of physiologically active substances, including the glutathione system.The aim of the study – to investigate the activity of glutathione peroxidase (GP), glutathione reductase (GR), as well as the content of reduced (GSH) and oxidized (GSSG) glutathione in liver, adipose tissue, and blood erythrocytes in experimental alimentary obesity.Research Methods. The experimental model of alimentary obesity was reproduced in 48 white non-linear male rats by using a food drive inducer-glutamic acid sodium salt in a ratio of 0.6: 100.0 and a high-calorie diet. GSH and GSSG activity were determined by the Elman method, GR activity was measured by the Ramos-Martines method, GP by Mills method. The protein concentration in the supernatants of the homogenate tissues was evaluated by the Lowry method.Results and Discussion. The obtained data indicates a decrease in the level of GSH after 14 days of the experiment in all the tissues studied. The same trend was observed in the animals of the second experimental group: the GSH index decreased by 36.1 % in the blood and, correspondingly, by 52.8 % and 33.3 % in adipose tissue and liver (p <0.05). The GSSG index changed after 28 days of the experiment, namely increased relative to control. Reduction in the concentration of GSH in rats with alimentary obesity was due to a lack of the studied enzymes of the glutathione system: GP and GR involved in the regeneration of GSH with GSSG.Conclusions. The data indicate a reduction in overall capacity of glutathione system in rat tissues in case of alimentary obesity, as evidenced by the reduction of glutathione and GSH / GSSG ratio. Significant inhibition of enzymes of glutathione in animals with alimentary obesity (glutathione reductase and glutathione peroxidase) indicates their inability to fully confront the damaging effect of excessive lipid peroxidation products.
Вплив чотирихлористого вуглецю на стан вільнорадикальних процесів організму щурів та морфологічні зміни у товстій кишці
Authors: Pryshlyak A. M. , Yavorska S. I. , Holovatа Т. К. , Reminetskyy B. Y.
Published: July 2017

Introduction. Increased admission of herbal compounds in organism of humans and animals can trigger the development of functional disorders and pathological changes of the digestive system and in particular the colon.The aim of the study – tо evaluate the state of free radical processes and morphological changes in the colon with toxic experimental animals exposed by carbon tetrachloride.Research Methods. The study was performed on 44 white male rats weighing 180–200 g which were divided into 4 groups: group 1 – control (almost healthy animals); group 2–4 – rats with simulated toxic lesion by CCl4. Intragastric CCl4 was administered in 50.0 % oil solution at a rate of 0.2 ml of pure substance per100 g of body weight. The intensity of free radical processes evaluated with the level of malondialdehyde and diene conjugates, determined using spectrophotometric techniques; antioxidant system – with the activity of catalase in blood. According to the conventional method histological preparations were made. For qualitative and morphometric analysis system of a visual analysis of images using camera Vision Color CCD program and Inter Video Win DVR UTHSCSA Image Tool were used.Results and Discussion. The results shows that animals carbon tetrachloride intoxication is accompanied by activation of free radical oxidation of lipids, as evidenced by the increase in blood serum of animal content as malondialdehyde (MDA) and diene conjugates (DC) throughout the experiment, with the maximum concentration observed in malondialdehyde 7 days after poisoning. Under the influence of CC14 catalase activity increases in serum at the second, seventh and fourteenth days of the experiment in 1.3, 1.2 and 2.4 times respectively. Morphometric techniques revealed a significant restructuring of the mucosa, submucosa, muscular layer and serous membrane of the colon, accompanied by severe vascular disorders of alterative, infiltrative processes and changes of morphometric parameters of the colon’s wall structures at tissue and organ levels.Conclusions. In the case of CCl4 damage, the processes of free radical oxidation take place, the accumulation of toxic products of lipid peroxidation in the blood and the weakening of the enzyme system of antioxidant protection occur. A significant structural and morphometric reconstruction of the mucosa, submucosa, muscular and serous membranes of the colon has been established.