bluuebunny/crossref_metadata_2025 huggingface dataset:
The unfolded protein response and cellular senescence. A Review in the Theme: Cellular Mechanisms of Endoplasmic Reticulum Stress Signaling in Health and Disease
Authors: Pluquet Olivier , Pourtier Albin , Abbadie Corinne
Published: December 2014

The endoplasmic reticulum (ER) is a multifunctional organelle critical for the proper folding and assembly of secreted and transmembrane proteins. Perturbations of ER functions cause ER stress, which activates a coordinated system of transcriptional and translational controls called the unfolded protein response (UPR), to cope with accumulation of misfolded proteins and proteotoxicity. It results in ER homeostasis restoration or in cell death. Senescence is a complex cell phenotype induced by several stresses such as telomere attrition, DNA damage, oxidative stress, and activation of some oncogenes. It is mainly characterized by a cell enlargement, a permanent cell-cycle arrest, and the production of a secretome enriched in proinflammatory cytokines and components of the extracellular matrix. Senescent cells accumulate with age in tissues and are suspected to play a role in age-associated diseases. Since senescence is a stress response, the question arises of whether an ER stress could occur concomitantly with senescence and participate in the onset or maintenance of the senescent features. Here, we described the interconnections between the UPR signaling and the different aspects of the cellular senescence programs and discuss the implication of UPR modulations in this context.
Considerations when quantitating protein abundance by immunoblot
Authors: McDonough Alicia A. , Veiras Luciana C. , Minas Jacqueline N. , Ralph Donna Lee
Published: December 2014

The development of the immunoblot to detect and characterize a protein with an antisera, even in a crude mixture, was a breakthrough with wide-ranging and unpredictable applications across physiology and medicine. Initially, this technique was viewed as a tool for qualitative, not quantitative, analyses of proteins because of the high number of variables between sample preparation and detection with antibodies. Nonetheless, as the immunoblot method was streamlined and improved, investigators pushed it to quantitate protein abundance in unpurified samples as a function of treatment, genotype, or pathology. This short review, geared at investigators, reviewers, and critical readers, presents a set of issues that are of critical importance for quantitative analysis of protein abundance: 1) Consider whether tissue samples are of equivalent integrity and assess how handling between collection and assay influences the apparent relative abundance. 2) Establish the specificity of the antiserum for the protein of interest by providing clear images, molecular weight markers, positive and negative controls, and vendor details. 3) Provide convincing evidence for linearity of the detection system by assessing signal density as a function of sample loaded. 4) Recognize that loading control proteins are rarely in the same linear range of detection as the protein of interest; consider protein staining of the gel or blot. In summary, with careful attention to sample integrity, antibody specificity, linearity of the detection system, and acceptable loading controls, investigators can implement quantitative immunoblots to convincingly assess protein abundance in their samples.
Validation of a rapid, semiautomatic image analysis tool for measurement of gastric accommodation and emptying by magnetic resonance imaging
Authors: Banerjee Sreerup , Dixit Sudeepa , Fox Mark , Pal Anupam
Published: December 2014

Magnetic resonance imaging (MRI) has advantages for the assessment of gastrointestinal structures and functions; however, processing MRI data is time consuming and this has limited uptake to a few specialist centers. This study introduces a semiautomatic image processing system for rapid analysis of gastrointestinal MRI. For assessment of simpler regions of interest (ROI) such as the stomach, the system generates virtual images along arbitrary planes that intersect the ROI edges in the original images. This generates seed points that are joined automatically to form contours on each adjacent two-dimensional image and reconstructed in three dimensions (3D). An alternative thresholding approach is available for rapid assessment of complex structures like the small intestine. For assessment of dynamic gastrointestinal function, such as gastric accommodation and emptying, the initial 3D reconstruction is used as reference to process adjacent image stacks automatically. This generates four-dimensional (4D) reconstructions of dynamic volume change over time. Compared with manual processing, this semiautomatic system reduced the user input required to analyze a MRI gastric emptying study (estimated 100 vs. 10,000 mouse clicks). This analysis was not subject to variation in volume measurements seen between three human observers. In conclusion, the image processing platform presented processed large volumes of MRI data, such as that produced by gastric accommodation and emptying studies, with minimal user input. 3D and 4D reconstructions of the stomach and, potentially, other gastrointestinal organs are produced faster and more accurately than manual methods. This system will facilitate the application of MRI in gastrointestinal research and clinical practice.
Colon distention induces persistent visceral hypersensitivity by mechanotranscription of pain mediators in colonic smooth muscle cells
Authors: Lin You-Min , Fu Yu , Wu Chester C. , Xu Guang-Yin , Huang Li-Yen , Shi Xuan-Zheng
Published: December 2014

Abdominal pain and distention are major complaints in irritable bowel syndrome. Abdominal distention is mainly attributed to intraluminal retention of gas or solid contents, which may cause mechanical stress to the gut wall. Visceral hypersensitivity (VHS) may account for abdominal pain. We sought to determine whether tonic colon distention causes persistent VHS and if so whether mechanical stress-induced expression (mechanotranscription) of pain mediators in colonic smooth muscle cells (SMCs) plays a role in VHS. Human colonic SMCs were isolated and stretched in vitro to investigate whether mechanical stress upregulates expression of the pain mediator cyclooxygenase-2 (COX-2). Rat colon was distended with a 5-cm-long balloon, and gene expression of COX-2, visceromotor response (VMR), and sensory neuron excitability were determined. Static stretch of colonic SMCs induced marked expression of COX-2 mRNA and protein in a force- and time-dependent manner. Subnoxious tonic distention of the distal colon at ∼30–40 mmHg for 20 or 40 min induced COX-2 expression and PGE2 production in colonic smooth muscle, but not in the mucosa layer. Lumen distention also increased VMR in a force- and time-dependent manner. The increase of VMR persisted for at least 3 days. Patch-clamp experiments showed that the excitability of colon projecting sensory neurons in the dorsal root ganglia was markedly augmented, 24 h after lumen distention. Administration of COX-2 inhibitor NS-398 partially but significantly attenuated distention-induced VHS. In conclusion, tonic lumen distention upregulates expression of COX-2 in colonic SMC, and COX-2 contributes to persistent VHS.
Upregulation of bile acid receptor TGR5 and nNOS in gastric myenteric plexus is responsible for delayed gastric emptying after chronic high-fat feeding in rats
Authors: Zhou Hui , Zhou Shiyi , Gao Jun , Zhang Guanpo , Lu Yuanxu , Owyang Chung
Published: December 2014

Chronic high-fat feeding is associated with functional dyspepsia and delayed gastric emptying. We hypothesize that high-fat feeding upregulates gastric neuronal nitric oxide synthase (nNOS) expression, resulting in delayed gastric emptying. We propose this is mediated by increased bile acid action on bile acid receptor 1 (TGR5) located on nNOS gastric neurons. To test this hypothesis, rats were fed regular chow or a high-fat diet for 2 wk. Rats fed the high-fat diet were subjected to concurrent feeding with oral cholestyramine or terminal ileum resection. TGR5 and nNOS expression in gastric tissue was measured by immunohistochemistry, PCR, and Western blot. Gastric motility was assessed by organ bath and solid-phase gastric emptying studies. The 2-wk high-fat diet caused a significant increase in neurons coexpressing nNOS and TGR5 in the gastric myenteric plexus and an increase in nNOS and TGR5 gene expression, 67 and 111%, respectively. Enhanced nonadrenergic, noncholinergic (NANC) relaxation, deoxycholic acid (DCA)-induced inhibition in fundic tissue, and a 26% delay in gastric emptying accompanied these changes. A 24-h incubation of whole-mount gastric fundus with DCA resulted in increased nNOS and TGR5 protein expression, 41 and 37%, respectively. Oral cholestyramine and terminal ileum resection restored the enhanced gastric relaxation, as well as the elevated nNOS and TGR5 expression evoked by high-fat feeding. Cholestyramine also prevented the delay in gastric emptying. We conclude that increased levels of circulatory bile acids induced by high-fat feeding upregulate nNOS and TGR5 expression in the gastric myenteric plexus, resulting in enhanced NANC relaxation and delayed gastric emptying.
Induction of rhythmic transient depolarizations associated with waxing and waning of slow wave activity in intestinal smooth muscle
Authors: Pawelka Andrew J. , Huizinga Jan D.
Published: December 2014

Cannon described in 1902 the segmentation motor activity of the small intestine (Canon WB. J Med Res 7: 72–75, 1902). This motor pattern can arise when low-frequency transient depolarizations are evoked in the interstitial cells of Cajal associated with the deep muscular plexus (ICC-DMP) network, which then affect the omnipresent slow wave activity: changing its regular amplitude into a waxing and waning pattern. The objective of the present study was to investigate physiological stimuli that could induce the low-frequency component. Intracellular recordings were obtained from circular muscle with or without attached mucosa. Decanoic acid (1 mM) and butyric acid (10 mM) both evoked low-frequency transient depolarizations but through different mechanisms. Decanoic acid-induced waxing and waning was initiated by purely myogenic means when perfused onto exposed circular muscle. Butyric acid required the intact mucosa and uninhibited neural activity to elicit the low-frequency response. Evidence is provided that the transient rhythmic depolarizations occur in the absence of interstitial cells of Cajal associated with the myenteric plexus (ICC-MP). Onset of the slow transient depolarizations was stimulated by addition of Nω-nitro-l-arginine (l-NNA; 100 μM); thus the low-frequency component seems to be under chronic inhibition by nitric oxide. Excitatory tachykinergic stimulation induced the low-frequency component since substance P (0.5 μM) evoked it in the presence of neural blockade. In summary, interplay between two networks of myogenic pacemakers, neural activity, and nutrient factors such as fatty acids plays a role in the generation of the rhythmic low-frequency component that is essential for the development of the checkered segmentation motor pattern.
TNF-α increases endothelial progenitor cell adhesion to the endothelium by increasing bond expression and affinity
Authors: Prisco Anthony R. , Prisco Michael R. , Carlson Brian E. , Greene Andrew S.
Published: December 2014

Endothelial progenitor cells (EPCs) are a rare population of cells that participate in angiogenesis. To effectively use EPCs for regenerative therapy, the mechanisms by which they participate in tissue repair must be elucidated. This study focused on the process by which activated EPCs bind to a target tissue. It has been demonstrated that EPCs can bind to endothelial cells (ECs) through the tumore necrosis factor-α (TNF-α)-regulated vascular cell adhesion molecule 1/very-late antigen 4 (VLA4) interaction. VLA4 can bind in a high or low affinity state, a process that is difficult to experimentally isolate from bond expression upregulation. To separate these processes, a new parallel plate flow chamber was built, a detachment assay was developed, and a mathematical model was created that was designed to analyze the detachment assay results. The mathematical model was developed to predict the relative expression of EPC/EC bonds made for a given bond affinity distribution. EPCs treated with TNF-α/vehicle were allowed to bind to TNF-α/vehicle-treated ECs in vitro. Bound cells were subjected to laminar flow, and the cellular adherence was quantified as a function of shear stress. Experimental data were fit to the mathematical model using changes in bond expression or affinity as the only free parameter. It was found that TNF-α treatment of ECs increased adhesion through bond upregulation, whereas TNF-α treatment of EPCs increased adhesion by increasing bond affinity. These data suggest that injured tissue could potentially increase recruitment of EPCs for tissue regeneration via the secretion of TNF-α.
Thioredoxin-deficient mice, a novel phenotype sensitive to ambient air and hypersensitive to hyperoxia-induced lung injury
Authors: Das Kumuda C.
Published: December 2014

Pulmonary oxygen toxicity is a major clinical problem for patients undergoing supplemental oxygen therapy. Thioredoxin (Trx) is an endogenous antioxidant protein that regenerates oxidatively inactivated proteins. We examined how Trx contributes to oxygen tolerance by creating transgenic mice with decreased levels of functional thioredoxin (dnTrx-Tg) using a dominant-negative approach. These mice showed decreased Trx activity in the lung although the expression of mutant protein is three times higher than the wild-type mice. Additionally, we found that these mice showed increased oxidation of endogenous Trx in room air. When exposed to hyperoxia (>90% O2) for 4 days, they failed to recover and showed significant mortality. Even in normal oxygen levels, these mice displayed a significant decrease in aconitase and NADH dehydrogenase activities, decreased mitochondrial energy metabolism, increased p53 and Gadd45α expression, and increased synthesis of proinflammatory cytokines. These effects were further increased by hyperoxia. We also generated mice overexpressing Trx (Trx-Tg) and found they maintained lung redox balance during exposure to high oxygen and thus were resistant to hyperoxia-induced lung injury. These mice had increased levels of reduced Trx in the lung in normoxia as well as hyperoxia. Furthermore, the levels of aconitase and NADH dehydrogenase activities were maintained in these mice concomitant with maintenance of mitochondrial energy metabolism. The genotoxic stress markers such as p53 or Gadd45α remained in significantly lower levels in hyperoxia compared with dnTrx-Tg or wild-type mice. These studies establish that mice deficient in functional Trx exhibit a phenotype of sensitivity to ambient air and hypersensitivity to hyperoxia.
Significant mechanical interactions at physiological lengths and relative positions of rat plantar flexors
Authors: Bernabei Michel , van Dieën Jaap H. , Baan Guus C. , Maas Huub
Published: December 2014

In situ studies involving supraphysiological muscle lengths and relative positions have shown that connective tissue linkages connecting adjacent muscles can transmit substantial forces, but the physiological significance is still subject to debate. The present study investigates effects of such epimuscular myofascial force transmission in the rat calf muscles. Unlike previous approaches, we quantified the mechanical interaction between the soleus (SO) and the lateral gastrocnemius and plantaris complex (LG+PL) applying a set of muscle lengths and relative positions corresponding to the range of knee and ankle angles occurring during normal movements. In nine deeply anesthetized Wistar rats, the superficial posterior crural compartment was exposed, and distal and proximal tendons of LG+PL and the distal SO tendon were severed and connected to force transducers. The target muscles were excited simultaneously. We found that SO active and passive tendon force was substantially affected by proximally lengthening of LG+PL mimicking knee extension (10% and 0.8% of maximal active SO force, respectively; P < 0.05). Moreover, SO relative position significantly changed the LG+PL length-force relationship, resulting in nonunique values for passive slack-length and optimum-length estimates. We conclude that also, for physiological muscle conditions, isometric force of rat triceps surae muscles is determined by its muscle-tendon unit length as well as by the length and relative position of its synergists. This has implications for understanding the neuromechanics of skeletal muscle in normal and pathological conditions, as well as for studies relying on the assumption that muscles act as independent force actuators.
Menthol suppresses laryngeal C-fiber hypersensitivity to cigarette smoke in a rat model of gastroesophageal reflux disease: the role of TRPM8
Authors: Liu Bi-Yu , Lin Yu-Jung , Lee Hung-Fu , Ho Ching-Yin , Ruan Ting , Kou Yu Ru
Published: December 2014

Patients with gastroesophageal reflux disease (GERD) display enhanced laryngeal reflex reactivity to stimuli that may be due to sensitization of the laryngeal C-fibers by acid and pepsin. Menthol, a ligand of transient receptor potential melastatin-8 (TRPM8), relieves throat irritation. However, the possibility that GERD induces laryngeal C-fiber hypersensitivity to cigarette smoke (CS) and that menthol suppresses this event has not been investigated. We delivered CS into functionally isolated larynxes of 160 anesthetized rats. Laryngeal pH 5-pepsin treatment, but not pH 5-denatured pepsin, augmented the apneic response to CS, which was blocked by denervation or perineural capsaicin treatment (a procedure that blocks the conduction of C fibers) of the superior laryngeal nerves. This augmented apnea was partially attenuated by capsazepine [an transient receptor potential vanilloid 1 (TRPV1) antagonist], SB-366791 (a TRPV1 antagonist), and HC030031 [a transient receptor potential ankyrin 1 (TRPA1) antagonist] and was completely prevented by a combination of TRPV1 and TRPA1 antagonists. Local application of menthol significantly suppressed the augmented apnea and this effect was reversed by pretreatment with AMTB (a TRPM8 antagonist). Our electrophysiological studies consistently revealed that laryngeal pH 5-pepsin treatment increased the sensitivity of laryngeal C-fibers to CS. Likewise, menthol suppressed this laryngeal C-fiber hypersensitivity and its effect could be reversed by pretreatment with AMTB. Our results suggest that laryngeal pH 5-pepsin treatment increases sensitivity to CS of both TRPV1 and TRPA1, which are presumably located at the terminals of laryngeal C-fibers. This sensory sensitization leads to enhanced laryngeal reflex reactivity and augmentation of the laryngeal C-fiber responses to CS, which can be suppressed by menthol acting via TRPM8.
TWEAK-Fn14 pathway activation after exercise in human skeletal muscle: insights from two exercise modes and a time course investigation
Authors: Raue Ulrika , Jemiolo Bozena , Yang Yifan , Trappe Scott
Published: December 2014

The cell surface receptor Fn14/TWEAKR was recently reported by our laboratory to be a prominent marker in the resistance exercise (RE) induced Transcriptome. The purpose of the present study was to extend our Transcriptome findings and investigate the gene and protein expression time course of markers in the TWEAK-Fn14 pathway following RE or run exercise (RUN). Vastus lateralis muscle biopsies were obtained from 6 RE subjects [25 ± 4 yr, 1-repetition maximum (RM): 99 ± 27 kg] pre- and 0, 1, 2, 4, 8, 12, and 24 h post RE (3 × 10 at 70% 1-RM). Lateral gastrocnemius biopsies were obtained from 6 RUN subjects [25 ± 4 yr, maximum oxygen uptake (V̇o2max): 63 ± 8 ml·kg−1·min−1] pre- and 0, 1, 2, 4, 8, 12, and 24 h after a 30-min RUN (75% V̇o2max). After RE, Fn14 gene and protein expression were induced ( P < 0.05) and peaked at 8 and 12 h, respectively. Downstream markers analyzed showed evidence of TWEAK-Fn14 signaling through the alternative NF-κB pathway after RE. After RUN, Fn14 gene expression was induced ( P < 0.05) to a much lesser extent and peaked at 24 h. Fn14 protein expression was only measurable on a sporadic basis, and there was weak evidence of alternative NF-κB pathway signaling after RUN. TWEAK gene and protein expression were not influenced by either exercise mode. These are the first human data to show a transient activation of the TWEAK-Fn14 axis in the recovery from exercise, and our data suggest the level of activation is exercise mode dependent. Furthermore, our collective data support a myogenic role for TWEAK-Fn14 through the alternative NF-κB pathway in human skeletal muscle.
Characterizing rapid-onset vasodilation to single muscle contractions in the human leg
Authors: Credeur Daniel P. , Holwerda Seth W. , Restaino Robert M. , King Phillip M. , Crutcher Kiera L. , Laughlin M. Harold , Padilla Jaume , Fadel Paul J.
Published: December 2014

Rapid-onset vasodilation (ROV) following single muscle contractions has been examined in the forearm of humans, but has not yet been characterized in the leg. Given known vascular differences between the arm and leg, we sought to characterize ROV following single muscle contractions in the leg. Sixteen healthy men performed random ordered single contractions at 5, 10, 20, 40, and 60% of their maximum voluntary contraction (MVC) using isometric knee extension made with the leg above and below heart level, and these were compared with single isometric contractions of the forearm (handgrip). Single thigh cuff compressions (300 mmHg) were utilized to estimate the mechanical contribution to leg ROV. Continuous blood flow was determined by duplex-Doppler ultrasound and blood pressure via finger photoplethysmography (Finometer). Single isometric knee extensor contractions produced intensity-dependent increases in peak leg vascular conductance that were significantly greater than the forearm in both the above- and below-heart level positions (e.g., above heart level: leg 20% MVC, +138 ± 28% vs. arm 20% MVC, +89 ± 17%; P < 0.05). Thigh cuff compressions also produced a significant hyperemic response, but these were brief and smaller in magnitude compared with single isometric contractions in the leg. Collectively, these data demonstrate the presence of a rapid and robust vasodilation to single muscle contractions in the leg that is largely independent of mechanical factors, thus establishing the leg as a viable model to study ROV in humans.
Changes in the leukocyte methylome and its effect on cardiovascular-related genes after exercise
Authors: Denham Joshua , O'Brien Brendan J. , Marques Francine Z. , Charchar Fadi J.
Published: December 2014

Physical exercise has proven cardiovascular benefits, yet there is no clear understanding of the related molecular mechanisms leading to this. Here we determined the beneficial epigenetic effects of exercise after sprint interval training, a form of exercise known to improve cardiometabolic health. We quantified genome-wide leukocyte DNA methylation of 12 healthy young (18–24 yr) men before and after 4 wk (thrice weekly) of sprint interval training using the 450K BeadChip (Illumina) and validated gene expression changes in an extra seven subjects. Exercise increased subjects' cardiorespiratory fitness and maximal running performance, and decreased low-density lipoprotein cholesterol concentration in conjunction with genome-wide DNA methylation changes. Notably, many CpG island and gene promoter regions were demethylated after exercise, indicating increased genome-wide transcriptional changes. Among genes with DNA methylation changes, epidermal growth factor ( EGF), a ligand of the epidermal growth factor receptor known to be involved in cardiovascular disease, was demethylated and showed decreased mRNA expression. Additionally, we found that in microRNAs miR-21 and miR-210, gene DNA methylation was altered by exercise causing a cascade effect on the expression of the mature microRNA involved in cardiovascular function. Our findings demonstrate that exercise alters DNA methylation in circulating blood cells in microRNA and protein-coding genes associated with cardiovascular physiology.
Human perceptual overestimation of whole body roll tilt in hypergravity
Authors: Clark Torin K. , Newman Michael C. , Oman Charles M. , Merfeld Daniel M. , Young Laurence R.
Published: December 2014

Hypergravity provides a unique environment to study human perception of orientation. We utilized a long-radius centrifuge to study perception of both static and dynamic whole body roll tilt in hypergravity, across a range of angles, frequencies, and net gravito-inertial levels (referred to as G levels). While studies of static tilt perception in hypergravity have been published, this is the first to measure dynamic tilt perception (i.e., with time-varying canal stimulation) in hypergravity using a continuous matching task. In complete darkness, subjects reported their orientation perception using a haptic task, whereby they attempted to align a hand-held bar with their perceived horizontal. Static roll tilt was overestimated in hypergravity, with more overestimation at larger angles and higher G levels, across the conditions tested (overestimated by ∼35% per additional G level, P < 0.001). As our primary contribution, we show that dynamic roll tilt was also consistently overestimated in hypergravity ( P < 0.001) at all angles and frequencies tested, again with more overestimation at higher G levels. The overestimation was similar to that for static tilts at low angular velocities but decreased at higher angular velocities ( P = 0.006), consistent with semicircular canal sensory integration. To match our findings, we propose a modification to a previous Observer-type canal-otolith interaction model. Specifically, our data were better modeled by including the hypothesis that the central nervous system treats otolith stimulation in the utricular plane differently than stimulation out of the utricular plane. This modified model was able to simulate quantitatively both the static and the dynamic roll tilt overestimation in hypergravity measured experimentally.
Testosterone modulates preattentive sensory processing and involuntary attention switches to emotional voices
Authors: Chen Chenyi , Chen Chin-Yau , Yang Chih-Yung , Lin Chi-Hung , Cheng Yawei
Published: December 2014

Testosterone is capable of altering facial threat processing. Voices, similar to faces, convey social information. We hypothesized that administering a single dose of testosterone would change voice perception in humans. In a placebo-controlled, randomly assigned, double-blind crossover design, we administered a single dose of testosterone or placebo to 18 healthy female volunteers and used a passive auditory oddball paradigm. The mismatch negativity (MMN) and P3a in responses to fearfully, happily, and neutrally spoken syllables dada and acoustically matched nonvocal sounds were analyzed, indicating preattentive sensory processing and involuntary attention switches. Results showed that testosterone administration had a trend to shorten the peak latencies of happy MMN and significantly enhanced the amplitudes of happy and fearful P3a, whereas the happy- and fearful-derived nonvocal MMN and P3a remained unaffected. These findings demonstrated acute effect of testosterone on the neural dynamics of voice perception. Administering a single dose of testosterone modulates preattentive sensory processing and involuntary attention switches in response to emotional voices.
The Effect of Hydroxyl Moieties and Their Oxosubstitution on Bile Acid Association Studied in Floating Monolayers
Authors: Szekeres Márta , Viskolcz Béla , Poša Mihalj , Csanádi János , Škorić Dušan , Illés Erzsébet , Tóth Ildikó Y. , Tombácz Etelka
Published: December 2014

Bile salt aggregates are promising candidates for drug delivery vehicles due to their unique fat-solubilizing ability. However, the toxicity of bile salts increases with improving fat-solubilizing capability and so an optimal combination of efficient solubilization and low toxicity is necessary. To improve hydrophilicity (and decrease toxicity), we substituted hydroxyl groups of several natural bile acid (BA) molecules for oxogroups and studied their intrinsic molecular association behavior. Here we present the comparative Langmuir trough study of the two-dimensional (2D) association behavior of eight natural BAs and four oxoderivatives (traditionally called keto-derivatives) floated on an aqueous subphase. The series of BAs and derivatives showed systematic changes in the shape of the compression isotherms. Two types of association could be distinguished: the first transition was assigned to the formation of dimers through H-bonding and the second to the hydrophobic aggregation of BA dimers. Hydrophobic association of BA molecules in the films is linked to the ability of forming H-bonded dimers. Both H-bond formation and hydrophobic association weakened with increasing number of hydroxyl groups, decreasing distance between hydroxyl groups, and increasing oxosubstitution. The results also show that the Langmuir trough method is extremely useful in selecting appropriate BA molecules to design drug delivery systems.
Evaluation of 11 Scoring Functions Performance on Matrix Metalloproteinases
Authors: Shamsara Jamal
Published: December 2014

Matrix metalloproteinases (MMPs) have distinctive roles in various physiological and pathological processes such as inflammatory diseases and cancer. This study explored the performance of eleven scoring functions (D-Score, G-Score, ChemScore, F-Score, PMF-Score, PoseScore, RankScore, DSX, and X-Score and scoring functions of AutoDock4.1 and AutoDockVina). Their performance was judged by calculation of their correlations to experimental binding affinities of 3D ligand-enzyme complexes of MMP family. Furthermore, they were evaluated for their ability in reranking virtual screening study results performed on a member of MMP family (MMP-12). Enrichment factor at different levels and receiver operating characteristics (ROC) curves were used to assess their performance. Finally, we have developed a PCA model from the best functions. Of the scoring functions evaluated, F-Score, DSX, and ChemScore were the best overall performers in prediction of MMPs-inhibitors binding affinities while ChemScore, Autodock, and DSX had the best discriminative power in virtual screening against the MMP-12 target. Consensus scorings did not show statistically significant superiority over the other scorings methods in correlation study while PCA model which consists of ChemScore, Autodock, and DSX improved overall enrichment. Outcome of this study could be useful for the setting up of a suitable scoring protocol, resulting in enrichment of MMPs inhibitors.
New Computing Technology in Reliability Engineering
Authors: Briš Radim , Domesová Simona
Published: December 2014

Reliability engineering is relatively new scientific discipline which develops in close connection with computers. Rapid development of computer technology recently requires adequate novelties of source codes and appropriate software. New parallel computing technology based on HPC (high performance computing) for availability calculation will be demonstrated in this paper. The technology is particularly effective in context with simulation methods; nevertheless, analytical methods are taken into account as well. In general, basic algorithms for reliability calculations must be appropriately modified and improved to achieve better computation efficiency. Parallel processing is executed by two ways, firstly by the use of the MATLAB function parfor and secondly by the use of the CUDA technology. The computation efficiency was significantly improved which is clearly demonstrated in numerical experiments performed on selected testing examples as well as on industrial example. Scalability graphs are used to demonstrate reduction of computation time caused by parallel computing.
Evaluation of Halogenated Coumarins for Antimosquito Properties
Authors: Narayanaswamy Venugopala K. , Gleiser Raquel M. , Kasumbwe Kabange , Aldhubiab Bandar E. , Attimarad Mahesh V. , Odhav Bharti
Published: December 2014

Mosquitoes are the major vectors of parasites and pathogens affecting humans and domestic animals. The widespread development of insecticide resistance and negative environmental effects of most synthetic compounds support an interest in finding and developing alternative products against mosquitoes. Natural coumarins and synthetic coumarin analogues are known for their several pharmacological properties, including being insecticidal. In the present study halogenated coumarins (3-mono/dibromo acetyl, 6-halogenated coumarin analogues) were screened for larvicidal, adulticidal, and repellent properties againstAnopheles arabiensis, a zoophilic mosquito that is one of the dominant vectors of malaria in Africa. Five compounds exerted 100% larval mortality within 24 h of exposure. All coumarins and halogenated coumarins reversibly knocked down adult mosquitoes but did not kill them after 24 h of exposure. Repellent properties could not be evidenced. Five compounds were considered potential larvicidal agents for further research and development, while adulticidal activity was considered only mild to moderate.
Betweenness Centrality in Some Classes of Graphs
Authors: Raghavan Unnithan Sunil Kumar , Kannan Balakrishnan , Jathavedan Madambi
Published: December 2014

There are several centrality measures that have been introduced and studied for real-world networks. They account for the different vertex characteristics that permit them to be ranked in order of importance in the network. Betweenness centrality is a measure of the influence of a vertex over the flow of information between every pair of vertices under the assumption that information primarily flows over the shortest paths between them. In this paper we present betweenness centrality of some important classes of graphs.
Determination of the Maximal Corrective Ability and Optimal Placement of the Ortho-SUV Frame for Femoral Deformity with respect to the Soft Tissue Envelope, a Biomechanical Modelling Study
Authors: Skomoroshko Petr V. , Vilensky Victor A. , Hammouda Ahmed I. , Fletcher Matt D. A. , Solomin Leonid N.
Published: December 2014

Circular fixation according to the Ilizarov method is a well-recognised modality of treatment for trauma and deformity. One shortcoming of the traditional fixator is its limited ability to correct more than one plane of deformity simultaneously, leading to lengthy frame-time indices. Hexapod circular fixation utilising computer guidance is commonplace for complex multidimensional deformity but difficulties often arise with correction of femoral deformity due to bulkiness of the frame construct, particularly in proximal deformity and in patients of increased size. The Ortho-SUV frame is an innovative hexapod which permits unique customisation to individual patient anatomy to maximise tolerance and optimal range of deformity correction. We hypothesised that the optimal configuration and maximal degree of correction achievable by the Ortho-SUV frame can be biomechanically modelled and applied clinically. A study was constructed using Ortho-SUV and femoral limb models to measure deformity correction via differing frame constructs and determine optimal frame configuration to achieve correction in proximal, middle, and distal third deformities with respect to the soft tissue envelope. The ideal frame configuration is determined for correction of deformity in all locations of the femur with the maximal parameters of correction calculated whilst avoiding and mitigating soft tissue irritation from bulky frame construction.
A Turn‐On Fluorescent Probe for Detecting Nitric Oxide in Aqueous Media
Authors: Koo Eunhae , Lee Jong-Chul
Published: December 2014

Imaging of nitric oxide (NO) in living cells can provide new insights in understanding unsolved pathways in the cardiovascular and neurological dysfunction and many types of cancers. For the detection of NO under physiological conditions, we synthesized a turn‐on fluorescent probe comprising CdSe/ZnS quantum dots (QDs) coordinated with dirhodium complex. Emission from CdSe/ZnS‐QDs is quenched when coordinated with the dirhodium complex but can be restored upon the displacement by nitric oxide.
On Cyclic Variability in a Residual Effected HCCI Engine with Direct Gasoline Injection during Negative Valve Overlap
Authors: Hunicz Jacek
Published: December 2014

This study contributes towards describing the nature of cycle‐by‐cycle variability in homogeneous charge compression ignition (HCCI) engines. Experimental measurements were performed using a single cylinder research engine operated in the negative valve overlap (NVO) mode and fuelled with direct gasoline injection. Both stoichiometric and lean mixtures were applied in order to distinguish between different exhaust‐fuel reactions during the NVO period and their propagation into the main event combustion. The experimental results show that the mode of cycle‐by‐cycle variability depends on the NVO phenomena. Under stoichiometric mixture conditions, neither variability in the main event indicated mean effective pressure (IMEP) nor the combustion timing was affected by the NVO phenomena; however, long period oscillations in IMEP were observed. In contrast, for lean mixture, where fuel oxidation during the NVO period took place, distinctive correlations between NVO phenomena and the main event combustion parameters were observed. A wavelet analysis revealed the presence of both long‐term and short‐term oscillations in IMEP, in accordance with the extent of NVO phenomena. Characteristic patterns in IMEP were recognized using an in‐house algorithm.
Dispersive Surface Energy and Acid-Base Parameters of Tosylate Functionalized Poly(ethylene glycol) via Inverse Gas Chromatography
Authors: Sesigur Feyza , Sakar Dolunay , Yazici Ozlem , Cakar Fatih , Cankurtaran Ozlem , Karaman Ferdane
Published: December 2014

An inverse gas chromatographic (IGC) study of the sorption properties of poly(ethylene glycol) modified with tosylate (PEG-TOS) was presented. PEG-TOS was synthesized via the tosylation of the corresponding poly(ethylene glycol) (PEG) withp-toluenesulfonyl chloride in the basic medium. The synthesized PEG-Tos was characterized by FTIR-ATR and1HNMR techniques. The retention diagrams of n-hexane, n-heptane, n-octane, n-nonane, n-decane, dichloromethane, chloroform, acetone, tetrahydrofuran, ethyl acetate, and ethanol on the PEG and PEG-Tos were plotted at temperatures in K between 303 and 373 by inverse gas chromatography technique. The dispersive component of the surface-free energy,γSD, of studied adsorbent surface was estimated using retention times of different nonpolar organics in the infinite dilution region. Thermodynamic parameters of adsorption (free energy,ΔGAS, enthalpy,ΔHAS, and entropy,ΔSAS), dispersive components of the surface energies,γSD, and the acid,KA, and base,KD, constants for the PEG and PEG-Tos were calculated and the results were discussed.
Female Sex Offenders and Pariah Femininities: Rewriting the Sexual Scripts
Authors: Hayes Sharon , Baker Bethney
Published: December 2014

This paper aims to analyze the way in which the media reports of sex offences tend to reinforce traditional sexual scripts and gender identities. Compared to investigations into male sex offenders, female sex offending is relatively underresearched, undertheorized, and misunderstood (Hayes and Carpenter, 2013). We argue that the media’s reinforcement of traditional scripts has hindered the development of awareness of sex offending by women, depicting them as aberrations, that is, as “female pariahs.” As Harris (2010) notes, female sex crimes cannot be explained by male theories of crime. To address this issue, we examined 487 media reports from Australia and the United Kingdom and found that, as key stakeholders in public debate, the media does indeed play a crucial role in shaping the public perceptions of female sex offenders as aberrations and pariahs. This distorted view influences approaches to understanding and acknowledging sex offending by women as well as hindering the safe and timely reporting of offences by victims.
Delusions of Disseminated Fungosis
Authors: Gassiep Ian , Griffin Paul Matthew
Published: December 2014

Introduction. Delusional infestation is a rare monosymptomatic hypochondriacal psychosis according to The Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5; American Psychiatric Association, 2013). It can be a primary disorder or associated with an underlying psychological or physical disorder. It commonly presents as delusional parasitosis, and less than 1% may be fungi related. We present this case as it is a rare presentation of a rare condition.Case Presentation. Our patient is a 60-year-old Caucasian man who presented with a 7-year history of delusional infestation manifested as a disseminated fungal infection. He had previously been reviewed by multiple physicians for the same with no systemic illness diagnosed. After multiple reviews and thorough investigation we diagnosed him with a likely delusional disorder. As is common with this patient cohort he refused psychiatric review or antipsychotic medication.Conclusion. A delusion of a disseminated fungal infestation is a rare condition. It is exceedingly difficult to treat as these patients often refuse to believe the investigation results and diagnosis. Furthermore, they either refuse or are noncompliant with treatment. Multidisciplinary outpatient evaluation may be the best way to allay patient fears and improve treatment compliance.
Ex Vivo Characterization of a Novel Iodine-123-Labelled Aminomethylchroman as a Potential Agonist Ligand for SPECT Imaging of Dopamine D2/3Receptors
Authors: van Wieringen Jan-Peter , de Bruin Kora , Janssen Henk M. , Fransen P. Michel , Janssen Anton G. M. , van Doremalen Peter A. , Michel Martin C. , Elsinga Philip H. , Booij Jan
Published: December 2014

For imaging of dopamine D2/3receptors, agonist tracers are favoured over antagonists because they are more sensitive to detection of dopamine release and because they may selectively label the high-affinity receptor state. We have developed novel D2/3receptor selective agonists that can be radiolabelled with [123I], which label is advantageous over most other labels, such as carbon-11, as it has a longer half-life. Particularly, we considered (R) N-[7-hydroxychroman-2-yl]-methyl 4-iodobenzyl amine (compound1) as an attractive candidate for development as it shows high binding affinity to D2/3receptors in vitro, and here we report on the characterization of this first [123I]-labelled D2/3receptor agonist radiopharmaceutical intended for SPECT imaging. The appropriate tin precursor for [123I]-1was developed and was successfully radiolabelled with iodine-123 giving a moderate yield (30–35%) and a good purity (>95%) for [123I]-1. In biodistribution experiments in Wistar rats intravenous injection of [123I]-1resulted in a fast brain uptake, where the observed binding in the D2/3receptor-rich striatum was slightly higher than that in the cerebellum 30 min to 4 h p.i. Storage phosphor imaging experiments, however, did not show specific D2/3receptor binding. In conclusion, despite promising in vitro data for1, neither specific ex vivo binding nor high signal-to-noise ratios were found in rodents for [123I]-1.
Ionic Liquid‐Assisted Synthesis of a NiO/CNTs Composite and Its Electrochemical Capacitance
Authors: Chen Yitong , Lu Xiangjun , Gao Bo
Published: December 2014

A novel solid‐state method has been developed for synthesizing nickel oxide (NiO)/carbon nanotubes (CNTs) composite using an ionic liquid (IL, 1‐butyl‐3‐methylimidazolium chloride) as the reaction medium. Ultraviolet‐visible (UV‐vis) absorbance spectroscopy, infrared spectroscopy (IR), and scanning electron microscopy (SEM) were employed to investigate the structure, morphology, and formation mechanism of the synthesized sample. The results demonstrated that the IL is effective for dispersing CNTs, which allows the tethering of nickel (II) ions onto the surfaces of the CNTs and facilitates the subsequent chemical deposition of NiO to obtain the NiO/CNTs composite. The electrochemical properties of the composite were determined using cyclic voltammetry and galvanostatic charge/discharge measurements in 6 M KOH. Because of its unique structure, the prepared NiO/CNTs electrode exhibited good capacitive behavior and cyclability. The high specific capacitance (521 F g−1) and good rate capability (91% capacity retention at 0.5 A g−1) of the NiO/CNTs composite enable its use as a practical supercapacitor electrode material.
Xiao Yao San Improves Depressive‐Like Behaviors in Rats with Chronic Immobilization Stress through Modulation of Locus Coeruleus‐Norepinephrine System
Authors: Ding Xiu-Fang , Zhao Xiao-Hua , Tao Yang , Zhong Wei-Chao , Fan Qin , Diao Jian-Xin , Liu Yuan-Liang , Chen Yu-Yao , Chen Jia-Xu , Lv Zhi-Ping
Published: December 2014

Most research focuses on the hypothalamic‐pituitary‐adrenal (HPA) axis, hypothalamus‐pituitary‐thyroid (HPT) axis, and hypothalamus‐pituitary‐gonadal (HPGA) axis systems of abnormalities of emotions and behaviors induced by stress, while no studies of Chinese herbal medicine such as Xiao Yao San (XYS) on the mechanisms of locus coeruleus‐norepinephrine (LC‐NE) system have been reported. Therefore, experiments were carried out to observe mechanism of LC‐NE system in response to chronic immobilization stress (CIS) and explore the antidepressant effect of XYS. Rat model was established by CIS. LC morphology in rat was conducted. The serum norepinephrine (NE) concentrations and NE biosynthesis such as tyrosine hydroxylase (TH), dopamine‐β‐hydroxylase (DBH), and corticotrophin‐releasing‐factor (CRF) in LC were determined. Results showed that there were no discernible alterations in LC in rats. The serum NE concentrations, positive neurons, mean optical density (MOD), and protein levels of TH, DBH, and CRF in model group were significantly increased compared to the control group. But XYS‐treated group displayed a significantly decreased in NE levels and expressions of TH, DBH, and CRF compared to the model group. In conclusion, CIS can activate LC‐NE system to release NE and then result in a significant decrease in rats. XYS treatment can effectively improve depressive‐like behaviors in rats through inhibition of LC‐NE neurons activity.
Sexually Transmitted Disease Partner Notification among African-American, Adolescent Women
Authors: Buchsbaum Anna , Gallo Maria F. , Whiteman Maura K. , Cwiak Carrie , Goedken Peggy , Kraft Joan Marie , Jamieson Denise J. , Kottke Melissa
Published: December 2014

Objective. To better understand preferences and practices regarding partner notification of sexually transmitted infection (STI) among female, African-American adolescents.Methods. Participants completed a questionnaire and STI testing at baseline. Those diagnosed with Chlamydia or gonorrhea were recruited for a follow-up study, involving another questionnaire and repeat STI testing after three months.Results. At baseline, most participants (85.1%) preferred to tell their partner about an STI diagnosis themselves instead of having a health care provider inform him, and 71.0% preferred to bring their partner for clinic treatment instead of giving him pills or a prescription. Two-thirds of participants were classified as having high self-efficacy for partner notification of a positive STI diagnosis. In the multivariable analysis, older participants and those with fewer lifetime sexual partners were more likely to have high self-efficacy. Ninety-three participants (26.6%) had Chlamydia or gonorrhea and, of this subset, 55 participated in the follow-up study. Most adolescents in the follow-up study (76.4%) notified their partner about their infection.Conclusion. Although participants were willing to use most methods of partner notification, most preferred to tell partners themselves and few preferred expedited partner therapy. Traditional methods for partner notification and treatment may not be adequate for all adolescents in this population.