bluuebunny/crossref_metadata_2025 huggingface dataset:
Bradykinin does not acutely sensitize the reflex pressor response during hindlimb skeletal muscle stretch in decerebrate rats
Authors: Rollins Korynne S. , Smith Joshua R. , Esau Peter J. , Kempf Evan A. , Hopkins Tyler D. , Copp Steven W.
Published: July 2017

Hindlimb skeletal muscle stretch (i.e., selective activation of the muscle mechanoreflex) in decerebrate rats evokes reflex increases in blood pressure and sympathetic nerve activity. Bradykinin has been found to sensitize mechanogated channels through a bradykinin B2 receptor-dependent mechanism. Moreover, bradykinin B2 receptor expression on sensory neurons is increased following chronic femoral artery ligation in the rat (a model of simulated peripheral artery disease). We tested the hypothesis that injection of bradykinin into the arterial supply of a hindlimb in decerebrate, unanesthetized rats would acutely augment (i.e., sensitize) the increase in blood pressure and renal sympathetic nerve activity during hindlimb muscle stretch to a greater extent in rats with a ligated femoral artery than in rats with a freely perfused femoral artery. The pressor response during static hindlimb muscle stretch was compared before and after hindlimb arterial injection of 0.5 µg of bradykinin. Injection of bradykinin increased blood pressure to a greater extent in “ligated” ( n = 10) than “freely perfused” ( n = 10) rats. The increase in blood pressure during hindlimb muscle stretch, however, was not different before vs. after bradykinin injection in freely perfused (14 ± 2 and 15 ± 2 mmHg for pre- and post-bradykinin, respectively, P = 0.62) or ligated (15 ± 3 and 14 ± 2 mmHg for pre- and post-bradykinin, respectively, P = 0.80) rats. Likewise, the increase in renal sympathetic nerve activity during stretch was not different before vs. after bradykinin injection in either group of rats. We conclude that bradykinin did not acutely sensitize the pressor response during hindlimb skeletal muscle stretch in freely perfused or ligated decerebrate rats.
Heterozygous loss-of-function mutation in Odd-skipped related 1 (Osr1) is associated with vesicoureteric reflux, duplex systems, and hydronephrosis
Authors: Fillion Marie-Lyne , El Andalousi Jasmine , Tokhmafshan Fatima , Murugapoopathy Vasikar , Watt Christine L. , Murawski Inga J. , Capolicchio John-Paul , El-Sherbiny Mohamed , Jednak Roman , Gupta Indra R.
Published: July 2017

Odd-skipped related 1 (Osr1) is a transcriptional repressor that plays critical roles in maintaining the mesenchymal stem cell population within the developing kidney. Here, we report that newborn pups with a heterozygous null mutation in Osr1 exhibit a 21% incidence of vesicoureteric reflux and have hydronephrosis and urinary tract duplications. Newborn pups have a short intravesical ureter, resulting in a less competent ureterovesical junction which arises from a delay in urinary tract development. We describe a new domain of Osr1 expression in the ureteral mesenchyme and within the developing bladder in the mouse. OSR1 was sequenced in 186 children with primary vesicoureteric reflux, and 17 have single nucleotide polymorphisms. Fifteen children have a common synonymous variant, rs12329305 , one child has a rare nonsynonymous variant, rs3440471 , and one child has a rare 5′-UTR variant, rs45535040 . The impact of these SNPs is not clear; therefore, the role of OSR1 in human disease remains to be elucidated. Osr1 is a candidate gene implicated in the pathogenesis of vesicoureteric reflux and congenital abnormalities of the kidney and urinary tract in mice.
ErbB4 deletion accelerates renal fibrosis following renal injury
Authors: Zeng Fenghua , Miyazawa Tomoki , Kloepfer Lance A. , Harris Raymond C.
Published: July 2017

Tubulointerstitial fibrosis (TIF) is a prominent factor in the progression of chronic kidney disease regardless of etiology. Avian erythroblastic leukemia viral oncogene homolog 4 (ErbB4) expression levels were inversely correlated to renal fibrosis in human fibrotic kidneys. In both unilateral ureteral obstruction (UUO) and ischemia-reperfusion injury followed by uninephrectomy (IRI/UNx) mouse models, expression levels of ErbB4 were elevated in the early stage of renal injury. Using mice with global ErbB4 deletion except for transgenic rescue in cardiac tissue ( ErbB4−/−ht+), we determined that UUO induced similar injury in proximal tubules compared with wild-type mice but more severe injury in distal nephrons. TIF was apparent earlier and was more pronounced following UUO in ErbB4−/−ht+ mice. With ErbB4 deletion, UUO injury inhibited protein kinase B phosphorylation and increased the percentage of cells in G2/M arrest. There was also increased nuclear immunostaining of yes-associated protein and increased expression of phospho-Mothers against decapentaplegic homolog 3, snail1, and vimentin. These results indicate that ErbB4 deletion accelerates the development and progression of renal fibrosis in obstructive nephropathy. Similar results were found in a mouse IRI/UNx model. In conclusion, increased expression of ErbB4 in the early stages of renal injury may reflect a compensatory effect to lessen tubulointerstitial injury.
Representing delayed force feedback as a combination of current and delayed states
Authors: Avraham Guy , Mawase Firas , Karniel Amir , Shmuelof Lior , Donchin Opher , Mussa-Ivaldi Ferdinando A. , Nisky Ilana
Published: July 2017

To adapt to deterministic force perturbations that depend on the current state of the hand, internal representations are formed to capture the relationships between forces experienced and motion. However, information from multiple modalities travels at different rates, resulting in intermodal delays that require compensation for these internal representations to develop. To understand how these delays are represented by the brain, we presented participants with delayed velocity-dependent force fields, i.e., forces that depend on hand velocity either 70 or 100 ms beforehand. We probed the internal representation of these delayed forces by examining the forces the participants applied to cope with the perturbations. The findings showed that for both delayed forces, the best model of internal representation consisted of a delayed velocity and current position and velocity. We show that participants relied initially on the current state, but with adaptation, the contribution of the delayed representation to adaptation increased. After adaptation, when the participants were asked to make movements with a higher velocity for which they had not previously experienced with the delayed force field, they applied forces that were consistent with current position and velocity as well as delayed velocity representations. This suggests that the sensorimotor system represents delayed force feedback using current and delayed state information and that it uses this representation when generalizing to faster movements.

NEW & NOTEWORTHY The brain compensates for forces in the body and the environment to control movements, but it is unclear how it does so given the inherent delays in information transmission and processing. We examined how participants cope with delayed forces that depend on their arm velocity 70 or 100 ms beforehand. After adaptation, participants applied opposing forces that revealed a partially correct representation of the perturbation using the current and the delayed information.
Emergent cortical circuit dynamics contain dense, interwoven ensembles of spike sequences
Authors: Dechery Joseph B. , MacLean Jason N.
Published: July 2017

Temporal codes are theoretically powerful encoding schemes, but their precise form in the neocortex remains unknown in part because of the large number of possible codes and the difficulty in disambiguating informative spikes from statistical noise. A biologically plausible and computationally powerful temporal coding scheme is the Hebbian assembly phase sequence (APS), which predicts reliable propagation of spikes between functionally related assemblies of neurons. Here, we sought to measure the inherent capacity of neocortical networks to produce reliable sequences of spikes, as would be predicted by an APS code. To record microcircuit activity, the scale at which computation is implemented, we used two-photon calcium imaging to densely sample spontaneous activity in murine neocortical networks ex vivo. We show that the population spike histogram is sufficient to produce a spatiotemporal progression of activity across the population. To more comprehensively evaluate the capacity for sequential spiking that cannot be explained by the overall population spiking, we identify statistically significant spike sequences. We found a large repertoire of sequence spikes that collectively comprise the majority of spiking in the circuit. Sequences manifest probabilistically and share neuron membership, resulting in unique ensembles of interwoven sequences characterizing individual spatiotemporal progressions of activity. Distillation of population dynamics into its constituent sequences provides a way to capture trial-to-trial variability and may prove to be a powerful decoding substrate in vivo. Informed by these data, we suggest that the Hebbian APS be reformulated as interwoven sequences with flexible assembly membership due to shared overlapping neurons.

NEW & NOTEWORTHY Neocortical computation occurs largely within microcircuits comprised of individual neurons and their connections within small volumes (<500 μm3). We found evidence for a long-postulated temporal code, the Hebbian assembly phase sequence, by identifying repeated and co-occurring sequences of spikes. Variance in population activity across trials was explained in part by the ensemble of active sequences. The presence of interwoven sequences suggests that neuronal assembly structure can be variable and is determined by previous activity.
Control of Energy Storage Systems for Aeronautic Applications
Authors: Canciello G. , Cavallo A. , Guida B.
Published: July 2017

Future aircraft will make more and more use of automated electric power system management onboard. Different solutions are currently being explored, and in particular the use of a supercapacitor as an intelligent energy storage device is addressed in this paper. The main task of the supercapacitor is to protect the electric generator from abrupt power changes resulting from sudden insertion or disconnection of loads or from loads with regenerative power capabilities, like electromagnetic actuators. A controller based on high-gain concepts is designed to drive a DC/DC converter connecting the supercapacitor to the main electric bus. Formal stability proofs are given for the resulting nonlinear system, and strong robustness results from the use of high-gain and variable structure control implementation. Moreover, detailed simulations including switching devices and electrical parasitic elements are provided for different working scenarios, showing the effectiveness of the proposed solution.
Concussion Incidence and Recurrence in Professional Australian Football Match-Play: A 14-Year Analysis
Authors: Gibbs Nathan , Watsford Mark
Published: July 2017

Background. Concussion incidence rates in professional Australian football may be underreported due to the injury classification definition. A myriad of factors contribute to concussion risk; however, there is limited long-term surveillance in Australian football. This study analysed concussion in one Australian football team over an extended period. Method. Match-play concussion injuries in one team (n=116 participants) were diagnosed and treated by the team physician over 14 years. Analysis of factors related to concussion including matches played, time of day and season, and return to play provided an insight into occurrence and recurrence rates. Results. 140 concussions were recorded (17.6 per 1000 player match hours). A strong relationship was evident between matches played and concussion incidence (r=0.70) and match conditions did not negatively affect the concussion rate. Whether an athlete returned to play in the same match or suffered a loss-of-consciousness concussion (p=0.84), their ensuing rate of concussion was not affected. Conclusion. Concussion in professional Australian football was related to the number of matches played. Further, neither previous incidence nor loss of consciousness affected future concussion risk. This study provides ecologically valid evidence of the concussion incidence rate in professional Australian football and has implications for the management of athletes sustaining concussion injuries.
Visual Three-Dimensional Reconstruction of Aortic Dissection Based on Medical CT Images
Authors: Duan Xiaojie , Chen Dandan , Wang Jianming , Shi Meichen , Chen Qingliang , Zhao He , Zuo Ruixue , Li Xiuyan , Wang Qi
Published: July 2017

With the rapid development of CT technology, especially the higher resolution of CT machine and a sharp increase in the amount of slices, to extract and three-dimensionally display aortic dissection from the huge medical image data became a challenging task. In this paper, active shape model combined with spatial continuity was adopted to realize automatic reconstruction of aortic dissection. First, we marked aortic feature points from big data sample library and registered training samples to build a statistical model. Meanwhile, gray vectors were sampled by utilizing square matrix, which set the landmarks as the center. Posture parameters of the initial shape were automatically adjusted by the method of spatial continuity between CT sequences. The contrast experiment proved that the proposed algorithm could realize accurate aorta segmentation without selecting the interested region, and it had higher accuracy than GVF snake algorithm (93.29% versus 87.54% on aortic arch, 94.30% versus 89.25% on descending aorta). Aortic dissection membrane was extracted via Hessian matrix and Bayesian theory. Finally, the three-dimensional visualization of the aortic dissection was completed by volume rendering based on the ray casting method to assist the doctors in clinical diagnosis, which contributed to improving the success rate of the operations.
Risk Factors Affecting the Severity of Full-Term Neonatal Retinal Hemorrhage
Authors: Yanli Zhang , Qi Zhao , Yu Lin , Haike Guo
Published: July 2017

Objective. The purpose of this study was to explore the underlying clinical factors associated with the degree of retinal hemorrhage (RH) in full-term newborns. Methods. A total of 3054 full-term infants were included in this study. Eye examinations were performed with RetCamIII within one week of birth for all infants. Maternal, obstetric, and neonatal parameters were compared between newborns with RH and controls. The RH group was divided into three sections (I, II, and III) based on the degree of RH. Results. RH was observed in 1202 of 3054 infants (39.36%) in this study. The quantity and proportion of newborns in groups I, II, and III were 408 (13.36%), 610 (19.97%), and 184 (6.03%), respectively. Spontaneous vaginal delivery (SVD), prolonged duration of second stage of labor, advanced maternal age, and neonatal intracranial hemorrhage positively correlated with aggravation of the degree of RH in newborns. Conversely, cesarean section was protective against the incidence of RH. Conclusions. SVD, prolonged duration of second stage of labor, advanced maternal age, and neonatal intracranial hemorrhage were potential risk factors for aggravation of the degree of RH in full-term infants. Accordingly, infants with these risk factors may require greater attention with respect to RH development.
LEPA: A Lightweight and Efficient Public Auditing Scheme for Cloud-Assisted Wireless Body Sensor Networks
Authors: Li Song , Cui Jie , Zhong Hong , Zhang Yiwen , He Qiang
Published: July 2017

From smart watch to remote healthcare system, wireless body sensor networks (WBSNs) play an important role in modern healthcare system. However, the weak capacity of devices has limited WBSNs development. Considering the huge processing and storage capacity of the cloud, it can be merged with WBSNs to make up for the deficiencies of weak capacity. Based on this consideration, the concept of cloud-assisted WBSNs has been proposed recently. In contrast to generic data, the data in cloud-assisted WBSNs will be used for providing medical diagnosis, so the integrity of data is very important because any modification will result in severe consequences such as misdiagnosis. The public auditing scheme could provide an efficient solution to check the data integrity remotely without downloading them. However, the traditional public auditing scheme for cloud cannot be used directly due to the high data density and weak processing capacity in WBSNs. So, in this paper, we proposed a lightweight and efficient public auditing scheme, LEPA, for cloud-assisted WBSNs. Compared with similar schemes, the WBSNs’ client only needs to do one symmetrical encryption with low computational cost in LEPA. Security proof shows that LEPA can resist two types of adversaries in random oracle model. The efficiency evaluation also shows that LEPA outperforms previous proposals.
Influence of the Number of Axial Bexarotene Ligands on the Cytotoxicity of Pt(IV) Analogs of Oxaliplatin
Authors: Nosova Yulia N. , Zenin Ilia V. , Maximova Varvara P. , Zhidkova Ekaterina M. , Kirsanov Kirill I. , Lesovaya Ekaterina A. , Lobas Anna A. , Gorshkov Mikhail V. , Kovaleva Olga N. , Milaeva Elena R. , Galanski Markus , Keppler Bernhard K. , Nazarov Alexey A.
Published: July 2017

We present the synthesis and cytotoxic potencies of new Pt(IV) complexes with bexarotene, an anticancer drug that induces cell differentiation and apoptosis via selective activation of retinoid X receptors. In these complexes bexarotene is positioned as an axial ligand. The complex of one bexarotene ligand attached to Pt(IV) oxaliplatin moiety was potent whereas its counterpart carrying two bexarotene ligands was inactive.
A New Generalization of the Lomax Distribution with Increasing, Decreasing, and Constant Failure Rate
Authors: Oguntunde Pelumi E. , Khaleel Mundher A. , Ahmed Mohammed T. , Adejumo Adebowale O. , Odetunmibi Oluwole A.
Published: July 2017

Developing new compound distributions which are more flexible than the existing distributions have become the new trend in distribution theory. In this present study, the Lomax distribution was extended using the Gompertz family of distribution, its resulting densities and statistical properties were carefully derived, and the method of maximum likelihood estimation was proposed in estimating the model parameters. A simulation study to assess the performance of the parameters of Gompertz Lomax distribution was provided and an application to real life data was provided to assess the potentials of the newly derived distribution. Excerpt from the analysis indicates that the Gompertz Lomax distribution performed better than the Beta Lomax distribution, Weibull Lomax distribution, and Kumaraswamy Lomax distribution.
Y-Split Recession of the Medial Rectus Muscle as a Secondary and/or Unilateral Procedure in the Treatment of Esotropia with Distance/Near Disparity
Authors: Wipf Monika , Priglinger Siegfried , Palmowski-Wolfe Anja
Published: July 2017

Introduction. In esotropia with larger angles > near than at distance, splitting of the medial rectus muscle has been suggested as a treatment option. Previous reports of bilateral medial rectus Y-splitting as a first intervention showed a reduction of the distance/near disparity with fewer side effects compared to posterior fixation surgery. We address whether a medial rectus Y-splitting as a secondary and/or a unilateral procedure also reduce distance/near disparity.Materials and Methods. We retrospectively reviewed the charts of four patients undergoing Y-split recession as a second and/or unilateral surgery. Main outcomes were distance/near disparity and squint angles.Results and Discussion.Three of the four patients had undergone unilateral Y-splitting of the medial rectus as a secondary surgery, three as a unilateral procedure. Mean distance/near disparity was reduced from 17 PD preoperatively to zero at the final follow-up (FU). Preoperative angles ranged from 45 PD to 66 PD at near and from 25 PD to 55 PD at distance. At the final FU, these angles ranged from 0 PD to 20 PD at near and at distance. Mean FU was 42 months (range: 12–60 months).Conclusion. Y-split recession as a secondary and/or unilateral surgery for distance/near esotropia can reduce distance/near disparity with good long-term results. Residual esotropia can be corrected by adding resection of the lateral rectus muscle.
Combined Respiratory Chain Deficiency and UQCC2 Mutations in Neonatal Encephalomyopathy: Defective Supercomplex Assembly in Complex III Deficiencies
Authors: Feichtinger René G. , Brunner-Krainz Michaela , Alhaddad Bader , Wortmann Saskia B. , Kovacs-Nagy Reka , Stojakovic Tatjana , Erwa Wolfgang , Resch Bernhard , Windischhofer Werner , Verheyen Sarah , Uhrig Sabine , Windpassinger Christian , Sternberg Felix , Makowski Christine , Strom Tim M. , Meitinger Thomas , Prokisch Holger , Sperl Wolfgang , Haack Tobias B. , Mayr Johannes A.
Published: July 2017

Vertebrate respiratory chain complex III consists of eleven subunits. Mutations in five subunits either mitochondrial (MT‐CYB) or nuclear (CYC1, UQCRC2, UQCRB, and UQCRQ) encoded have been reported. Defects in five further factors for assembly (TTC19, UQCC2, and UQCC3) or iron‐sulphur cluster loading (BCS1L and LYRM7) cause complex III deficiency. Here, we report a second patient with UQCC2 deficiency. This girl was born prematurely; pregnancy was complicated by intrauterine growth retardation and oligohydramnios. She presented with respiratory distress syndrome, developed epileptic seizures progressing to status epilepticus, and died at day 33. She had profound lactic acidosis and elevated urinary pyruvate. Exome sequencing revealed two homozygous missense variants in UQCC2, leading to a severe reduction of UQCC2 protein. Deficiency of complexes I and III was found enzymatically and on the protein level. A review of the literature on genetically distinct complex III defects revealed that, except TTC19 deficiency, the biochemical pattern was very often a combined respiratory chain deficiency. Besides complex III, typically, complex I was decreased, in some cases complex IV. In accordance with previous observations, the presence of assembled complex III is required for the stability or assembly of complexes I and IV, which might be related to respirasome/supercomplex formation.
Nanoparticles Decorated on Resin Particles and Their Flame Retardancy Behavior for Polymer Composites
Authors: Attia Nour F. , Zayed Mohamed
Published: July 2017

New nanocomposites have been developed by doping of amberlite IR120 resin with spherical TiO2 nanoparticles in the presence of maleate diphosphate. Polystyrene composites of resin, maleate diphosphate, and resin-maleate diphosphate were prepared individually. This is in addition to preparation of polymer nanocomposites of polystyrene-resin doped TiO2 nanoparticles-maleate diphosphate. The flame retardancy and thermal stability properties of these developed polymer composites were evaluated. The inclusion of resin and resin doped nanoparticles improved the fire retardant behavior of polystyrene composites and enhanced their thermal stability. Synergistic behavior between flame retardant, resin, and nanoparticles was detected. The rate of burning of the polymer nanocomposites was recorded as 10.7 mm/min achieving 77% reduction compared to pure polystyrene (46.5 mm/min). The peak heat release rate (PHRR) of the new polymer composites has reduced achieving 46% reduction compared to blank polymer. The morphology and dispersion of nanoparticles on resin and in polymer nanocomposites were characterized using transmission and scanning electron microscopy, respectively. The flame retardancy and thermal properties were evaluated using UL94 flame chamber, cone tests, and thermogravimetric analysis, respectively.
Inhibition of Rho Kinase Induces Antioxidative Molecules and Suppresses Reactive Oxidative Species in Trabecular Meshwork Cells
Authors: Fujimoto Tomokazu , Inoue Toshihiro , Ohira Saori , Awai-Kasaoka Nanako , Kameda Takanori , Inoue-Mochita Miyuki , Tanihara Hidenobu
Published: July 2017

Purpose. To investigate the effect of rho kinase inhibitors on oxidative stress in trabecular meshwork (TM) cells. Methods. TM cells were isolated from the eyes of cynomolgus monkeys. Y-27632 and menadione were used to inhibit rho kinase and induce production of reactive oxygen species (ROS), respectively. The cynomolgus monkey array and 12,613 probes were used in DNA microarray analysis, and the affected genes were categorized using gene ontology analysis. The mRNA levels of the target genes were confirmed by real-time RT-PCR. Intracellular oxidative stress was detected using a fluorescent reagent sensitive to ROS. Cell viability was assessed by the WST-8 assay. Results. Gene ontology analysis revealed upregulation of genes involved in antioxidant activity, and upregulation of catalase was confirmed by real-time RT-PCR after 30 min treatment with Y-27632. Production of ROS was increased by menadione, and the effect was partly suppressed by pretreatment with Y-27632. At a lower dose of menadione, Y-27632 stimulated TM cells and significantly increased their viability following menadione treatment compared to control cells. Conclusion. Using microarray analysis, Y-27632 was shown to upregulate antioxidative genes including catalase and partially reduce ROS production and cell death by oxidative stress caused by menadione.
Synthesis and Characterization of Mixed Iron-Manganese Oxide Nanoparticles and Their Application for Efficient Nickel Ion Removal from Aqueous Samples
Authors: Buccolieri Alessandro , Serra Antonio , Maruccio Giuseppe , Monteduro Anna Grazia , Padmanabhan Sanosh Kunjalukkal , Licciulli Antonio , Bonfrate Valentina , Salvatore Luca , Manno Daniela , Calcagnile Lucio , Giancane Gabriele
Published: July 2017

Mixed iron-manganese oxide nanoparticles, synthesized by a simple procedure, were used to remove nickel ion from aqueous solutions. Nanostructures, prepared by using different weight percents of manganese, were characterized by transmission electron microscopy, selected area diffraction, X-ray diffraction, Raman spectroscopy, and vibrating sample magnetometry. Adsorption/desorption isotherm curves demonstrated that manganese inclusions enhance the specific surface area three times and the pores volume ten times. This feature was crucial to decontaminate both aqueous samples and food extracts from nickel ion. Efficient removal of Ni2+ was highlighted by the well-known dimethylglyoxime test and by ICP-MS analysis and the possibility of regenerating the nanostructure was obtained by a washing treatment in disodium ethylenediaminetetraacetate solution.
Hsp72 and Nek6 Cooperate to Cluster Amplified Centrosomes in Cancer Cells
Authors: Sampson Josephina , O'Regan Laura , Dyer Martin J.S. , Bayliss Richard , Fry Andrew M.
Published: July 2017

Cancer cells frequently possess extra amplified centrosomes clustered into two poles whose pseudo-bipolar spindles exhibit reduced fidelity of chromosome segregation and promote genetic instability. Inhibition of centrosome clustering triggers multipolar spindle formation and mitotic catastrophe, offering an attractive therapeutic approach to selectively kill cells with amplified centrosomes. However, mechanisms of centrosome clustering remain poorly understood. Here, we identify a new pathway that acts through NIMA-related kinase 6 (Nek6) and Hsp72 to promote centrosome clustering. Nek6, as well as its upstream activators polo-like kinase 1 and Aurora-A, targeted Hsp72 to the poles of cells with amplified centrosomes. Unlike some centrosome declustering agents, blocking Hsp72 or Nek6 function did not induce formation of acentrosomal poles, meaning that multipolar spindles were observable only in cells with amplified centrosomes. Inhibition of Hsp72 in acute lymphoblastic leukemia cells resulted in increased multipolar spindle frequency that correlated with centrosome amplification, while loss of Hsp72 or Nek6 function in noncancer-derived cells disturbs neither spindle formation nor mitotic progression. Hence, the Nek6–Hsp72 module represents a novel actionable pathway for selective targeting of cancer cells with amplified centrosomes. Cancer Res; 77(18); 4785–96. ©2017 AACR.
MAPK Pathway and TERT Promoter Gene Mutation Pattern and Its Prognostic Value in Melanoma Patients: A Retrospective Study of 2,793 Cases
Authors: Bai Xue , Kong Yan , Chi Zhihong , Sheng Xinan , Cui Chuanliang , Wang Xuan , Mao Lili , Tang Bixia , Li Siming , Lian Bin , Yan Xieqiao , Zhou Li , Dai Jie , Guo Jun , Si Lu
Published: July 2017

Purpose: Ethnic differences are conspicuous in melanoma. This study is to obtain a comprehensive view of a genomic landscape and a better understanding of the correlations of gene mutation status with clinicopathologic characteristics and disease prognosis in the Asian population.

Experimental Design: A total of 2,793 melanoma patient samples were retrospectively collected and analyzed for mutations in C-KIT, BRAF, NRAS, and PDGFRA coding regions and telomerase reverse transcriptase (TERT) promoter region by Sanger sequencing. Mutations were correlated to clinicopathologic features and overall survival.

Results: The incidences of somatic mutations within the BRAF, NRAS, C-KIT, TERT-228, TERT-250, and PDGFRA genes were 23.7%, 10.4%, 8.0%, 5.9%, 5.5%, and 1.4%, respectively. Hotspot mutations accounted for 95.8% and 87.2% of BRAF and NRAS mutations, respectively; meanwhile, C-KIT and PDGFRA mutations showed more heterogeneity. BRAF, C-KIT, and NRAS mutations were mutually exclusive. BRAF, C-KIT, NRAS, and numbers of gene mutations of the MAPK pathway were all independent negative prognostic factors (P = 0.007, other P < 0.001, respectively). In acral melanoma, BRAF, C-KIT, and NRAS mutations were all independent prognostic factors of worse overall survival (all P < 0.001), whereas in mucosal melanoma, only C-KIT was (P = 0.006). Although correlated with BRAF mutations (P = 0.001 and P < 0.001 for C228T and C250T, respectively), TERT promoter gene mutations were not correlated with overall survival (P = 0.406 and 0.256, respectively).

Conclusions: The MAPK pathway and TERT promoter gene mutations are differentially represented in the Asian population. Mutations in BRAF, C-KIT, and NRAS have prognostic values that vary by melanoma subtypes. Clinical treatment targeting these critical pathways should be aimed directly at these poor-prognosis subpopulations for maximum potential impact. Clin Cancer Res; 23(20); 6120–7. ©2017 AACR.
Advanced Glycation End-Products Downregulate HoxA9EC through Activation of Nuclear Factor Kappa B by Reciprocal Interaction
Authors: Zhu Qian-qian , Li Dong-lin , He Yang-yan , Wu Zi-heng , Tian Lu , Zheng Cheng-fei , Zhang Nan , Zhang Hong-kun
Published: July 2017

Advanced glycation end-products (AGEs) have been recognized as an important pathophysiological mechanism in endothelial dysfunction during diabetic atherogenesis. Homeobox (Hox) genes have been identified as playing a regulatory role in the adult cardiovascular system. Regulation of HoxA9EC is involved in diabetic endothelial dysfunction, but the mechanism of HoxA9EC regulation has remained undefined. Here, we sought to investigate how HoxA9EC is regulated in AGE-induced endothelial dysfunction and to explore the mechanism involved. We used human umbilical venous endothelial cells (HUVECs) cocultured with AGEs, and examined endothelial nitric oxide synthase (eNOS) activation, nitric oxide (NO) release, cell migration, and the expression of HoxA9EC and nuclear factor kappa B (NF-κB). AGEs suppressed eNOS activation, NO release, and the migration of HUVECs. Knockout of HoxA9EC also reduced eNOS activation, NO release, and the migration of HUVECs, and the enhancement of HoxA9EC improved the function of HUVECs. Furthermore, AGEs downregulated HoxA9EC expression and activated NF-κB, and the depression of HoxA9EC was significantly attenuated by the NF-κB inhibitor. On the other hand, knockout of HoxA9EC activated NF-κB and the enhancement of HoxA9EC suppressed NF-κB activation. In conclusion, AGEs could induce endothelial dysfunction through NF-κB-dependent HoxA9EC downregulation by reciprocal interaction, and the enhancement of HoxA9EC expression could attenuate the impairment.
Inhibition of Necroptosis Attenuates Kidney Inflammation and Interstitial Fibrosis Induced By Unilateral Ureteral Obstruction
Authors: Xiao Xia , Du Chunyang , Yan Zhe , Shi Yonghong , Duan Huijun , Ren Yunzhuo
Published: July 2017

Background: Inflammation plays a crucial role in renal interstitial fibrosis, the pathway of chronic kidney diseases. Necroptosis is a novel form of regulated cell death, which plays a potential role in inflammation and renal diseases. The small molecule necrostatin-1 (Nec-1) is a specific inhibitor of necroptosis. This study was aimed at determining the role of necroptosis, RIP1/RIP3/mixed lineage kinase domain-like (MLKL) signaling pathway, in renal inflammation and interstitial fibrosis related to primitive tubulointerstitial injury. It was also aimed at evaluating the effect of Nec-1 in renal fibrosis induced by unilateral ureteral obstruction (UUO). Methods: Renal histology, immunohistochemistry, western blot, and real-time polymerase chain reaction were performed using UUO C57BL/6J mice model. Moreover, we tested whether Nec-1 was renal-protective in the interstitial fibrosis kidney. Mice were exposed to UUO and injected intraperitoneal with Nec-1 or vehicle. Results: The levels of RIP1/RIP3/MLKL protein and mRNA were increased in the obstructed kidneys 7 days after UUO; this was accompanied by changes in renal pathological lesions. Renal histological examination showed lesser renal damage in Nec-1-treated UUO mice. Renal inflammation, assessed by tumor necrosis factor-α, interleukin-1β, and monocyte chemotactic protein-1 was markedly attenuated by Nec-1. Furthermore, Nec-1 treatment also significantly reduced TGF-β and α-smooth muscle actin, indicating lesser renal interstitial fibrosis. Conclusion: These findings suggest that the participation of necroptosis in UUO is partly demonstrated. And necroptosis inhibition may have a potential role in the treatment of diseases with increased inflammatory response and interstitial fibrosis in renal.
Small Intestine Submucosa Is a Potential Material for Intrauterine Adhesions Treatment in a Rat Model
Authors: Kong Desheng , Zhang Lin , Xu Xin , Zhang Jingkun , Li Yanan , Huang Xianghua
Published: July 2017

Objective: To study whether small intestine submucosa (SIS) could be a treatment option for preventing the formation of intrauterine adhesions (IUAs). Methods: The IUAs model was established by mechanical curettage and infectious injury in a rat model. One uterine horn of the rat model was treated with the transplantation of SIS (SIS group) and the other one was left without any treatment (control group). The endometrium was evaluated with endometrial thickness, number of glands and fibrosis area. The endometrial receptive factors were detected by quantitative real-time polymerase chain reaction The number and location of embryos were documented to assess the function of endometrium. Results: In the SIS group, endometrial thickness was significantly thicker than that in the control group on the 14th and 21st day and the percentage of fibrosis area was significantly lower during the entire observation process (p < 0.05). The number of glands was similar between the 2 groups (p > 0.05). Receptive factors changed as follows: in the SIS group, the expression of uteroglobin was higher and peaked on the 21st day (3.42-fold, p < 0.05); the HOXA10 level was significantly higher on the 10th day (2.16-fold, p < 0.05), and it then decreased. More embryos were seen in SIS horns (5.13 vs. 1.25, p < 0.05). Conclusions: SIS could be a potential physical barrier for the formation of IUAs. It contributes to the regeneration of and improvement of the receptivity of endometrium, and helps in the implantation and development of embryos in a rat model.
Trigonelline Inhibits Inflammation and Protects β Cells to Prevent Fetal Growth Restriction during Pregnancy in a Mouse Model of Diabetes
Authors: Zhou Ji-Yin , Du Xiao-Huang , Zhang Zuo , Qian Gui-Sheng
Published: July 2017

Background: As an active component from traditional Chinese medicine, trigonelline has a protective effect on diabetes. This study evaluated the protective effects of trigonelline on diabetic mice during pregnancy. Methods: Diabetes was induced in female mice by intraperitoneal injection for continuous 5-day of 40 mg/kg/day streptozotocin. Female mice were divided into 4 groups after they were allowed to mate with normal male mice: nondiabetic, nondiabetic treated with trigonelline (70 mg/kg) for 18 days, diabetic, and diabetic treated with trigonelline (70 mg/kg). Results: Diabetic pregnant mice had significantly higher levels of blood glucose, serum total cholesterol, triglyceride, insulin, and leptin but lower serum omentin-1 level and insulin sensitivity index than the nondiabetic ones. Trigonelline improved the hyperglycemia, dyslipidemia, insulin resistance, and adipocytokine of diabetic pregnant mice. Diabetic pregnant mice had significantly reduced fetus numbers, fetal weight, and fetal/placental ratio, which were reversed by trigonelline. Trigonelline prevented the increase in proinflammatory cytokines and reduced interleukin-10 level in placenta of diabetic pregnant mice. Trigonelline increased β-cell replication and the decreased β-cell mass, and decreased the β-cell apoptosis of diabetic pregnant mice. Conclusion: These findings suggest that trigonelline protects diabetic pregnancy partly by suppressing inflammation, regulating the secretion of adipocytokines, increasing β-cell mass, replication, and decreasing β-cell apoptosis.
Загальні та місцеві фактори ризику виникнення основних стоматологічних захворювань у дітей, хворих на олігофренію
Authors: Zabolotny T. D. , Dutko G. Z.
Published: July 2017

Prevention of major dental diseases in children is one of the most urgent problems of dentistry in childhood. This is especially true in the category of children with central nervous system (CNS) disorders. It is known that deviations in the psychological development of children are often accompanied by somatic diseases. The literature highlights the dependence of dental status on somatic health.The aim of the study – to conduct an analysis of the somatic status of children with oligophrenic patients.Materials and Methods. The data presented during the examination of 263 children aged 12–18 years. The choice of this age group was subordinated to WHO (1997) requirements to obtain a reliable characterization of the state of solid dental tissues (group of children 12 years old) and periodontal tissues (group of children 15 years). A group of children 18 years old was selected to study the disease of hard tissues of teeth and periodontal tissues in the dynamics. Dental examination of this contingent of children was carried out at the psycho-neurological dispensary of the city of Lviv. The diagnosis of "oligophrenia" was established by a specialist of this specialty (psychiatrist). The control group included 99 students from several secondary schools in Lviv, of the same age, without psychoneurological abnormalities.Results and Discussion. Having conducted a detailed analysis of these indicators among the children of the main group, we have established their direct dependence on the severity of the underlying disease. According to the results of the research, in the main group there is a high percentage of children who were ill with infectious diseases (50 ± 3.9 %), indicating a decrease in the protective immune forces of the organism. Prevalent in the main group of children are diseases of the gastrointestinal tract. A significant number of children with oligophrenia who had a respiratory tract pathology (34.76 ± 3.72 %) were found. In addition to the general factors contributing to the occurrence of pathological processes in the tissues of the oral cavity, there are local, such as: anomalies of bite, dental arches, buckling of teeth, and the like.Conclusions. Some general and local risk factors for dental diseases characteristic of children with oligophrenia have been identified: pathological changes in the respiratory system (34.76 ± 3.72 %) and the gastrointestinal tract (32.32 ± 3.65 %) are more frequent than in mentally healthy children. Oral respiration is on the first place of the local factor of the occurrence of dental diseases in this contingent of children (59.15 ± 3.84 %). Particular weight is occupied by buccal pathology and teething brittleness (40.85 ± 3.84 %). We have also established the dependence of the general state of health of children-oligophrenic patients on the degree of reduction of their intelligence.
First record of Rhabdoblattella (Blaberidae, Epilamprinae) from China with descriptions of two new species
Authors: WANG ZHENZHEN , YANG RONG , WANG ZONGQING
Published: July 2017

Two new species (Rhabdoblattella hainanensis sp. n. and Rhabdoblattella disparis sp. n.) from Hainan and Yunnan Provinces, China are described and illustrated, which extends the geographical distribution of Rhabdoblattella northward from Vietnam. Photographs and detailed morphological descriptions including the male genitalia of R. hainanensis sp. n. and R. disparis sp. n. are given. For comparison, the photos of habitus and male genitalia of a closely related species, R. annamensis (Hanitsch, 1927) are provided. A key to all species of Rhabdoblattella is provided.
Low-Level Jets over Utö, Finland, Based on Doppler Lidar Observations
Authors: Tuononen Minttu , O’Connor Ewan J. , Sinclair Victoria A. , Vakkari Ville
Published: July 2017

Over two years of meteorological observations from Utö, a small island in the Finnish outer archipelago in the Baltic Sea, were used to investigate the occurrence and characteristics of low-level jets (LLJs) and the diurnal and seasonal variations in these properties. An objective LLJ identification algorithm that is suitable for high-temporal-and-vertical-resolution Doppler lidar data was created and applied to wind profiles obtained from a combination of Doppler lidar data and two-dimensional sonic anemometer observations. This algorithm was designed to identify coherent LLJ structures and requires that they persist for at least 1 h. The long-term mean LLJ frequency of occurrence at Utö was 12%, the mean LLJ wind speed was 11.6 m s−1, and the vast majority of identified LLJs occurred below 150 m above ground level. The LLJ frequency of occurrence was much higher during summer (21%) and spring (18%) than in autumn (8%) and winter (3%). During winter and spring, the LLJ frequency of occurrence is evenly distributed throughout the day. In contrast, the LLJ frequency of occurrence peaks at night (1900–0100 UTC) during summer and during the evening hours (1700–1900 UTC) in autumn. The highest and strongest LLJs come from the southwest, which is also the predominant LLJ direction in all seasons. LLJs below 100 m are common in spring and summer, are weaker, and do not show a strong directional dependence.
Momentum Flux of Convective Gravity Waves Derived from an Offline Gravity Wave Parameterization. Part I: Spatiotemporal Variations at Source Level
Authors: Kang Min-Jee , Chun Hye-Yeong , Kim Young-Ha
Published: July 2017

Spatiotemporal variations in momentum flux spectra of convective gravity waves (CGWs) at the source level (cloud top), including nonlinear forcing effects, are examined based on calculations using an offline version of CGW parameterization and global reanalysis data for a period of 32 years (1979–2010). The cloud-top momentum flux (CTMF) is not solely proportional to the convective heating rate but is affected by the wave-filtering and resonance factor and background stability and temperature underlying the convection. Consequently, the primary peak of CTMF is in the winter hemisphere midlatitudes, associated with storm tracks, where a secondary peak of convective heating exists, whereas the secondary peak of CTMF appears in the summer hemisphere tropics and intertropical convergence zone (ITCZ), where the primary peak of convective heating exists. The magnitude of CTMF fluctuates largely with 1-yr and 1-day periods in major CTMF regions. At low latitudes and Pacific storm-track regions, a 6-month period is also significant, and the decadal cycle appears in the southern Andes. The equatorial eastern Pacific region exhibits a substantial interannual to decadal scale of variabilities. The correlation between convective heating and the CTMF is relatively lower in the equatorial region than in other regions. The CTMF in 10°N–10°S during the period of the pre-Concordiasi campaign approximately follows a lognormal distribution but with a slight underestimation in the tail of the probability density function. In Part II, the momentum flux and drag of CGW in the stratosphere will be examined.
Shallow Precipitation Detection and Classification Using Multifrequency Radar Observations and Model Simulations
Authors: Arulraj Malarvizhi , Barros Ana P.
Published: July 2017

Detection of shallow warm rainfall remains a critical source of uncertainty in remote sensing of precipitation, especially in regions of complex topographic and radiometric transitions, such as mountains and coastlines. To address this problem, a new algorithm to detect and classify shallow rainfall based on space–time dual-frequency correlation (DFC) of concurrent W- and Ka-band radar reflectivity profiles is demonstrated using ground-based observations from the Integrated Precipitation and Hydrology Experiment (IPHEx) in the Appalachian Mountains (MV), United States, and the Biogenic Aerosols–Effects on Clouds and Climate (BAECC) in Hyytiala (TMP), Finland. Detection is successful with false alarm errors of 2.64% and 4.45% for MV and TMP, respectively, corresponding to one order of magnitude improvement over the skill of operational satellite-based radar algorithms in similar conditions. Shallow rainfall is misclassified 12.5% of the time at MV, but all instances of low-level reverse orographic enhancement are detected and classified correctly. The classification errors are 8% and 17% for deep and shallow rainfall, respectively, in TMP; the latter is linked to reflectivity profiles with dark band but insufficient radar sensitivity to light rainfall ( mm h−1) remains the major source of error. The potential utility of the algorithm for satellite-based observations in mountainous regions is explored using an observing system simulation (OSS) of concurrent CloudSat Cloud Profiling Radar (CPR) and GPM Dual-Frequency Precipitation Radar (DPR) during IPHEx, and concurrent satellite observations over Borneo. The results suggest that integration of the methodology in existing regime-based classification algorithms is straightforward, and can lead to significant improvements in the detection and identification of shallow precipitation.
Conflict and Cooperation: The Nordic Nuclear-Free Zone Today
Authors: Maude George
Published: July 2017

This article discusses three major lines of thinking about a proposed Nordic nuclear-free zone, namely the viewpoints of Olof Palme, Johan J⊘rgen Holst, and Osmo Apunen. These viewpoints constituted the key themes of the Nuclear Weapons and Northern Europe seminar held in Helsinki on 2–3 June 1983 under the auspices of the Finnish Institute of International Affairs. The article assumes the existence of a mounting degree of pressure in Northern Europe for such a zone and therefore attention is paid not to the question of the use-value of a NWFZ but to the method of its realization. It is concluded that notwithstanding the firm line taken by the present Norwegian government, NATO cannot — in the interests of its own power politics — long resist acceptance of a Nordic NWFZ. In this respect the article argues that the most acceptable model is the apparently least ambitious one.
LGBT Students Want Educators to Speak up for Them
Authors: Young Abe Louise
Published: July 2017

What do LGBT students wish teachers would do to make school safer? Read their four ideas, and get ready to make a difference.