bluuebunny/crossref_metadata_2025 huggingface dataset:
The-LHON-Enigma: explaining the behaviour of Leber’s Hereditary Optic Neuropathy by the use of a simple computer model
Authors: Logan Ian
Published: November 2013

Leber’s Hereditary Optic Neuropathy (LHON) appears as anenigmaticcondition; affecting only certain families and often causing a severe loss of vision seemingly at random amongst family members. The first breakthrough came in 1988 with the linking of the condition to a mutation in the mitochondrial DNA (mtDNA). Now it is known that about 90% of cases are linked to 3 mutations. In this paper thehypothesisis suggested that a LHON mutation decreases the function of the mitochondrial enzyme, Complex I, by 50% and this alone critically endangers the survival of cells - especially the fragile cells of the optic nerves. A computer model has been written to illustrate how thehypothesiscan produce anatural historyfor the condition of LHON that has features similar to those observed in practice; thereby successfully explaining the behaviour of thisenigmaticcondition.
Simultaneous optogenetic manipulation and calcium imaging in freely movingC. elegans
Authors: Shipley Frederick B. , Clark Christopher M. , Alkema Mark J. , Leifer Andrew M.
Published: November 2013

A fundamental goal of systems neuroscience is to probe the dynamics of neural activity that drive behavior. Here we present an instrument to simultaneously manipulate neural activity via Channelrhodopsin, monitor neural response via GCaMP3, and observes behavior in freely moving C. elegans. We use the instrument to directly observe the relation between sensory stimuli, interneuron activity and locomotion in the mechanosensory circuit. Now published as: Front Neural Circuits 8:28, doi:10.3389/fncir.2014.00028
An XA21-Associated Kinase (OsSERK2) regulates immunity mediated by the XA21 and XA3 immune receptors
Authors: Chen Xuewei , Zuo Shimin , Schwessinger Benjamin , Chern Mawsheng , Canlas Patrick E. , Ruan Deling , Zhou Xiaogang , Wang Jing , Daudi Arsalan , Petzold Christopher J. , Heazlewood Joshua L. , Ronald Pamela C.
Published: November 2013

The rice XA21 immune receptor kinase and the structurally related XA3 receptor, confer immunity toXanthomonas oryzaepv.oryzae(Xoo), the causal agent of bacterial leaf blight. Here we report the isolation of OsSERK2 (rice somatic embryogenesis receptor kinase 2) and demonstrate that OsSERK2 positively regulates immunity mediated by XA21 and XA3 as well as the rice immune receptor FLS2 (OsFLS2). Rice plants silenced forOsSerk2display altered morphology and reduced sensitivity to the hormone brassinolide. OsSERK2 interacts with the intracellular domains of each immune receptor in the yeast-two-hybrid system in a kinase activity dependent manner. OsSERK2 undergoes bidirectional trans-phosphorylation with XA21in vitroand forms a constitutive complex with XA21in vivo. These results demonstrate an essential role for OsSERK2 in the function of three rice immune receptors and suggest that direct interaction with the rice immune receptors is critical for their function. Taken together, our findings suggest that the mechanism of OsSERK2-meditated regulation of rice XA21, XA3 and FLS2 differs from that of AtSERK3/BAK1-mediated regulation of Arabidopsis FLS2 and EFR.
Functional connectivity networks with and without global signal correction
Authors: Hayasaka Satoru
Published: November 2013

In functional connectivity analyses in BOLD (blood oxygenation level dependent) fMRI data, there is an ongoing debate on whether to correct global signals in fMRI time series data. Although the discussion has been ongoing in the fMRI community since the early days of fMRI data analyses, this subject has gained renewed attention in recent years due to the surging popularity of functional connectivity analyses, in particular graph theory-based network analyses. However, the impact of correcting (or not correcting) for global signals has not been systematically characterized in the context of network analyses. Thus, in this work, I examined the effect of global signal correction on an fMRI network analysis. In particular, voxel-based resting-state fMRI networks were constructed with and without global signal correction. The resulting functional connectivity networks were compared. Without global signal correction, the distributions of the correlation coefficients were positively biased. I also found that, without global signal correction, nodes along the interhemisphic fissure were highly connected whereas some nodes and subgraphs around white-matter tracts became disconnected from the rest of the network. These results from this study show differences between the networks with or without global signal correction.
Clinical and regulatory implications of active run‐in phases in long‐term studies for bipolar disorder
Authors: Cipriani A. , Barbui C. , Rendell J. , Geddes J. R.
Published: November 2013

Objective

The integration of new treatments into the market and routine clinical practice should be dependent on robustness of evidence from randomised controlled trials (RCTs). We assessed study designs of long‐term studies for bipolar disorder of all second‐generation antipsychotics (SGAs) submitted to the Food and Drug Administration (FDA) and the completeness of evidence submitted to the regulatory agency.

Method

Systematic review of double‐blind RCTs comparing SGAs with placebo or active drugs in adults. FDA website and electronic databases were searched until July 2013.

Results

Six placebo‐controlled trials comparing aripiprazole, olanzapine, quetiapine and ziprasidone were found in the FDA website. Electronic searches found four additional RCTs about aripiprazole, olanzapine or quetiapine. All RCTs (either submitted to FDA or not) selected patients who responded to acute treatment to increase the treatment effect observed in the long‐term phase (enrichment design). By contrast, in the prescribing information sheets for all SGAs, the reported indication was ‘maintenance treatment of bipolar disorder’.

Conclusion

Extrapolation of results from enrichment studies to the more general population of patients should be carried out cautiously because average treatment benefits are likely to be less in unselected patients. Clear guidance for regulatory submission of RCTs is needed.
Secrets of platelet exocytosis – what do we really know about platelet secretion mechanisms?
Authors: Golebiewska Ewelina M. , Poole Alastair W.
Published: November 2013

Upon activation by extracellular matrix components or soluble agonists, platelets release in excess of 300 active molecules from intracellular granules. Those factors can both activate further platelets and mediate a range of responses in other cells. The complex microenvironment of a growing thrombus, as well as platelets' roles in both physiological and pathological processes, require platelet secretion to be highly spatially and temporally regulated to ensure appropriate responses to a range of stimuli. However, how this regulation is achieved remains incompletely understood. In this review we outline the importance of regulated secretion in thrombosis as well as in ‘novel’ scenarios beyond haemostasis and give a detailed summary of what is known about the molecular mechanisms of platelet exocytosis. We also discuss a number of theories of how different cargoes could be released in a tightly orchestrated manner, allowing complex interactions between platelets and their environment.
Macrophage inhibitory factor 1 acts as a potential biomarker in patients with esophageal squamous cell carcinoma and is a target for antibody‐based therapy
Authors: Wang Xiao‐Bing , Jiang Xing‐Ran , Yu Xi‐Ying , Wang Lin , He Shun , Feng Fei‐Yue , Guo Li‐Ping , Jiang Wei , Lu Shih‐Hsin
Published: November 2013

Macrophage inhibitory factor 1 (MIC1) is frequently altered in various cancers. The aim of this study was to investigate the clinical significance of MIC1 for esophageal squamous cell carcinoma (ESCC). Serum MIC1 of 286 ESCC and 250 healthy subjects was detected, the diagnostic performance was assessed and compared with SCC, CEA, CA199 and CA724, and the value as a prognostic indicator was also evaluated. The expression of MIC1 in ESCC cell lines, tissues were detected, and the inhibition of MIC1 antibody on ESCC was carried out in vitro and in vivo. The results showed that the serum MIC1 of ESCC was significantly higher than normal groups (P < 0.001), and was positively associated with tumor invasion (P = 0.030) as well as lymph node metastasis (P = 0.007). The sensitivity of MIC1 was significantly better than SCC, CEA, CA199 and CA724, especially for stage I ESCC. Patients with higher serum MIC1 also had a poorer prognosis in relapse‐free (P = 0.050) and tumor‐specific survival (P = 0.005). In vitro studies showed that the expression of MIC1 was upregulated in 37.5% (3/8) ESCC cell lines and 45% (18/40) tissues, and the transcription of MIC1 in tumor tissues was significantly higher than paired adjacent normal tissues (P = 0.001). The antibody of MIC1 inhibited the tumor growth (P < 0.001), and showing preference for tumor tissues in xenograft model. The decreased formation of neovascularization lumen may be involved in the mechanism. We conclude that MIC1 plays an important role in the progression of ESCC and can serve as a potential biomarker and therapeutic target for ESCC.
Suppression of Tregs by anti‐glucocorticoid induced TNF receptor antibody enhances the antitumor immunity of interferon‐α gene therapy for pancreatic cancer
Authors: Aida Kouichirou , Miyakawa Reina , Suzuki Koji , Narumi Kenta , Udagawa Takeshi , Yamamoto Yuki , Chikaraishi Tatsuya , Yoshida Teruhiko , Aoki Kazunori
Published: November 2013

We have reported that interferon (IFN)‐α can attack cancer cells by multiple antitumor mechanisms including the induction of direct cancer cell death and the enhancement of an immune response in several pancreatic cancer models. However, an immunotolerant microenvironment in the tumors is often responsible for the failure of the cancer immunotherapy. Here we examined whether the suppression of regulatory T cells (Tregs) within tumors can enhance an antitumor immunity induced by an intratumoral IFN‐α gene transfer. First we showed that an intraperitoneal administration of an agonistic anti‐glucocorticoid induced TNF receptor (GITR) monoclonal antibody (mAb), which is reported to suppress the function of Tregs, significantly inhibited subcutaneous tumor growth in a murine pancreatic cancer model. The anti‐GITR mAb was then combined with the intratumoral injection of the IFN‐α‐adenovirus vector. The treatment with the antibody synergistically augmented the antitumor effect of IFN‐α gene therapy not only in the vector‐injected tumors but also in the vector‐uninjected tumors. Immunostaining showed that the anti‐GITR mAb decreased Foxp3+ cells infiltrating in the tumors, while the intratumoral IFN‐α gene transfer increased CD4+ and CD8+ T cells in the tumors. Therefore, the combination therapy strongly inclined the immune balance of the tumor microenvironment in an antitumor direction, leading to a marked systemic antitumor effect. The CCR5 expression on Tregs was downregulated in the antibody‐treated mice, which may explain the decrease of tumor‐infiltrating Tregs. The combination of Treg‐suppression by GITR mAb and the tumor immunity induction by IFN‐α gene therapy could be a promising therapeutic strategy for pancreatic cancer.
Image Space Rendering of Point Clouds Using the HPR Operator
Authors: Machado e Silva R. , Esperança C. , Marroquim R. , Oliveira A. A. F.
Published: November 2013

The hidden point removal (HPR) operator introduced by Katz et al. [KTB07] provides an elegant solution for the problem of estimating the visibility of points in point samplings of surfaces. Since the method requires computing the three‐dimensional convex hull of a set with the same cardinality as the original cloud, the method has been largely viewed as impractical for real‐time rendering of medium to large clouds. In this paper we examine how the HPR operator can be used more efficiently by combining several image space techniques, including an approximate convex hull algorithm, cloud sampling, and GPU programming. Experiments show that this combination permits faster renderings without overly compromising the accuracy.
Modelling of Non‐Periodic Aggregates Having a Pile Structure
Authors: Sakurai K. , Miyata K.
Published: November 2013

This paper presents a procedure for modelling aggregates such as piles that consist of arbitrary components. The method generates an aggregate of components that need to be accumulated, and an aggregate shape represents the surface of the target aggregate. The number of components and their positions and orientations are controlled by five parameters. The components, the aggregate shape and the parameters are the inputs for the method which involves placement and refinement steps. In the placement step, the orientation and initial position of a component are determined by a non‐periodic placement such that each component overlaps its neighbours. In the refinement step, to construct a pile structure, the position of each component is adjusted by reducing the overlap.
On Perception of Semi‐Transparent Streamlines for Three‐Dimensional Flow Visualization
Authors: Mishchenko O. , Crawfis R.
Published: November 2013

One of the standard techniques to visualize three‐dimensional flow is to use geometry primitives. This solution, when opaque primitives are used, results in high levels of occlusion, especially with dense streamline seeding. Using semi‐transparent geometry primitives can alleviate the problem of occlusion. However, with semi‐transparency some parts of the data set become too vague and blurry, while others are still heavily occluded. We conducted a user study that provided us with results on perceptual limits of using semi‐transparent geometry primitives for flow visualization. Texture models for semi‐transparent streamlines were introduced. Test subjects were shown multiple overlaying layers of streamlines and recorded how many different flow directions they were able to perceive. The user study allowed us to identify a set of top scoring textures. We discuss the results of the user study, provide guidelines on using semi‐transparency for three‐dimensional flow visualization and show how varying textures for different streamlines can further enhance the perception of dense streamlines. We also discuss the strategies for dealing with very high levels of occlusion. The strategies are per‐pixel filtering of flow directions, when only some of the streamlines are rendered at a particular pixel, and opacity normalization, a way of altering the opacity of overlapping streamlines with the same direction. We illustrate our results with a variety of visualizations.
Occupational airborne contact dermatitis from benzodiazepines and other drugs
Authors: Swinnen Inge , Ghys Katrien , Kerre Stefan , Constandt Lieve , Goossens An
Published: November 2013

Background

Healthcare workers (or relatives) crushing drug tablets for patients with difficulties in swallowing are at risk of developing sensitization via airborne exposure. Tetrazepam, in particular, is increasingly being described as an important occupational allergen in this regard, although other drugs are also involved.

Objectives

To identify the allergenic culprits in 4 patients, namely 2 nurses, 1 pharmacy assistant, and 1 spouse, who all regularly crushed tablets of systemic drugs and presented with severe airborne dermatitis.

Methods

The patients were patch tested with all of the drugs that they handled, as well as with potential cross‐sensitizing molecules.

Results

All 4 patients reacted to tetrazepam and other benzodiazepines, some of which they had not previously come into contact with, which favours cross‐reactivity rather than concomitant sensitization. These patients also had positive reactions to several other non‐structurally related drugs for which, in some cases, there was no history of exposure.

Conclusions

Subjects having to crush drugs, in either an occupational or a non‐occupational context, and who present with dermatitis suspected of being airborne‐induced, should be patch tested with all contacted medicaments, as well as with possible cross‐reacting molecules. Prevention by the use of crushing devices and protective measures (gloves and masks) when medications are handled should be advised.
Synthesis of methine dyes derived from indol‐2‐ones and their dyeability on polyester fibres
Authors: Qi Zhen , Ailin Yuan , Chunling Zheng , Shuyuan Bai , Haibo Wang
Published: November 2013

Three series of methine dyes were synthesised by the condensation of indol‐2‐ones with aryl acroleins. The structures of these dyes were confirmed by 1H nuclear magnetic resonance spectroscopy, infrared spectrometry and elemental analysis. The ultraviolet‐visible absorption spectra of the dyes were examined in different solvents. The maximum absorption wavelength ranged from 386 to 495 nm. The dyes were applied to polyester fibres, and the colour gamut and dyeing properties were investigated. Results showed that the dye uptake (percentage exhaustion) was 86.9–92.0%, with the hue changing from yellow to red. The rubbing fastness, wash fastness, and sublimation fastness were between 4 and 5.
The correlation between the interference colour and growth procedure of anodic titanium dioxide nanotube arrays
Authors: Moon Jongyun , Kemell Marianna , Park Byungki , Suominen Arho , Mäkilä Ermei , Punkkinen Risto , Hedman Hannu‐Pekka , Kim Hong , Lassila Lippo V , Tuominen Aulis
Published: November 2013

Titanium dioxide nanotube arrays were anodised from titanium foils in an aqueous electrolyte solution of hydrofluoric acid. The formed oxide showed visually different colours owing to light interference in the titanium dioxide layer. The behaviour of interference colour in anodic titanium dioxide film was investigated by varying anodisation parameters such as the applied voltage and the anodisation time. The morphologies and the crystalline phases of anodised samples were studied on a field emission scanning electron microscope and X‐ray diffractometer. The correlation between the interference colour and growth procedure of anodic titanium dioxide nanotube arrays was studied. The anodic films prepared under different conditions consisted of a compact oxide film with a nanoporous/tubular structure upon/beneath it. The crystalline phase of the anodic oxide layer was amorphous. The optical properties of the oxide film were investigated on a spectrophotometer. Optical interference could be detected in compact oxide layers when the thickness of the titanium dioxide was as small as 70 nm. In general, the interferences of the nanoporous/tubular structures were lower than those for compact structures. The empirical colour properties were estimated by the L*a*b* system. The relationships between the interference colour of anodic titanium dioxide film and its thickness and morphology are discussed.
Punctate pemphigus: an underreported direct immunofluorescence pattern
Authors: Ko Christine J. , McNiff Jennifer M.
Published: November 2013

Intercellular epidermal deposition of immunoglobulin G (IgG) in a continuous net‐like or ‘chicken wire’ pattern is a well‐described and diagnostic finding in direct immunofluorescence (DIF) studies of pemphigus. In our experience, punctate or dot‐like intercellular deposition of IgG can also be seen in cases of pemphigus but has received little attention in the literature. We describe a series of DIF specimens showing intercellular deposition of IgG in continuous and/or punctate patterns, which occurred with equal frequency in pemphigus vulgaris and pemphigus foliaceus. This series highlights the punctate or dot‐like pattern of intercellular IgG deposition in DIF studies of pemphigus, reviews potential mechanisms and calls attention to this potentially under‐recognized phenomenon.
Eradication of cats (Felis catus) from subantarctic Macquarie Island
Authors: Robinson Susan A. , Copson Geoffrey R.
Published: November 2013

The feral Cat (Felis catus) population on Macquarie Island was targeted for eradication between 1996 and 2002, with 761 cats captured during this period. After 22 years of cat control from 1974 integrated with control programmes for other pests, effort intensified for 2 years before a dedicated eradication programme began in 1998. The primary knock‐down for the eradication used cage trapping and shooting, with most surviving cats captured with leg‐hold traps. A total of 6298 field days and 216 574 trap nights were recorded in this operation. Factors contributing to the success of the programme included extensive planning, increased staff numbers at critical times, better access to remote areas of the island, introduction of leg‐hold traps, sufficient operational funding and good collaboration between government agencies operating on the island. The programme would have benefited from earlier deployment of detector dogs and better posteradication monitoring of a broader range of native species impacted by cats. The successful eradication of cats from Macquarie Island, being the second largest achieved to date, provides valuable experience for cat eradication attempts on other large remote islands. This programme relied on ground‐based techniques with minimal use of poisons and provides possible options for sites where broad‐scale poisoning, or where aerial distribution of poisons, cannot be used.
Understanding fisheries credit systems: potentials and pitfalls of managing catch efficiency
Authors: Van Riel Maria C , Bush Simon R , van Zwieten Paul A M , Mol Arthur P J
Published: November 2013

Following implementation in a range of other resource sectors, a number of credit‐like systems have been proposed for fisheries. But confusion exists over what constitutes these nascent ‘fisheries credit’ systems and how they operate. Based on a review of credit systems in other sectors, this study fills this gap by defining how credit systems function and what credits add to prevailing fisheries management. In doing so, we distinguish ‘mitigation’ and ‘behavioural’ fishery credits. Mitigation credits require resource users to compensate for unsustainable catches of target species, by‐catch species or damaging practices on the marine environment by investing in conservation in a biologically equivalent habitat or resource. Behavioural credit systems incentivize fishers to gradually change their fishing behaviour to more sustainable fishing methods by rewarding them with, for instance, extra fishing effort to compensate for less efficient but more sustainable fishing methods. The choice of credit system largely depends on the characteristics of specific fisheries and the management goals agreed upon by managers, scientists and the fishing industry. The study concludes that fisheries credit systems are different but complimentary to other forms of management by focusing on ‘catchability’ or gear efficiency in addition to effort or catch quota, affecting overall economic efficiency by setting specific goals as to how fish are caught. Credit systems therefore incentivize specific management interventions that can directly improve stock sustainability, conserve habitat and endangered species, or decrease by‐catch.
The reprogramming factor nuclear receptor subfamily 5, group A, member 2 cannot replace octamer‐binding transcription factor 4 function in the self‐renewal of embryonic stem cells
Authors: Choi Kyeng‐Won , Oh Hye‐rim , Lee Jaeyoung , Lim Bobae , Han Yong‐Mahn , Oh Junseo , Kim Jungho
Published: November 2013

Although octamer‐binding transcription factor 4 (Oct‐4) is one of the most intensively studied factors in mammalian development, no cellular genes capable of replacing Oct‐4 function in embryonic stem (ES) cells have been found. Recent data show that nuclear receptor subfamily 5, group A, member 2 (Nr5a2) is able to replace Oct‐4 function in the reprogramming process; however, it is unclear whether Nr5a2 can replace Oct‐4 function in ES cells. In this study, the ability of Nr5a2 to maintain self‐renewal and pluripotency in ES cells was investigated. Nr5a2 localized to the nucleus in ES cells, similarly to Oct‐4. However, expression of Nr5a2 failed to rescue the stem cell phenotype or to maintain the self‐renewal ability of ES cells. Furthermore, as compared with Oct‐4‐expressing ES cells, Nr5a2‐expressing ES cells showed a reduced number of cells in S‐phase, did not expand normally, and did not remain in an undifferentiated state. Ectopic expression of Nr5a2 in ES cells was not able to activate transcription of ES cell‐specific genes, and gene expression profiling demonstrated differences between Nr5a2‐expressing and Oct‐4‐expressing ES cells. In addition, Nr5a2‐expressing ES cells were not able to form teratomas in nude mice. Taken together, these results strongly suggest that the gene regulation properties of Nr5a2 and Oct‐4 and their abilities to confer self‐renewal and pluripotency of ES cells differ. The present study provides strong evidence that Nr5a2 cannot replace Oct‐4 function in ES cells.
Peculiar monomeric interferon gammas, IFNγrel 1 and IFNγrel 2, in ginbuna crucian carp
Authors: Shibasaki Yasuhiro , Yabu Takeshi , Araki Kyosuke , Mano Nobuhiro , Shiba Hajime , Moritomo Tadaaki , Nakanishi Teruyuki
Published: November 2013

The existence of fish‐specific isoforms of interferon (IFN)γ, known as IFNγ‐related (IFNγrel), has been reported in several fish species. However, comparisons with deduced amino acid sequences of known IFNγrels among several fish species have indicated significant differences at the C‐terminus basic amino acid continuous sequences, which indicate the existence of multiple IFNγrel isoforms. Two distinct cDNAs, encoding two IFNγrels, ifngrel 1 and ifngrel 2, were cloned from ginbuna crucian carp (Carassius auratus langsdorfii). Recombinant IFNγrel 1 and IFNγrel 2 have shown high antiviral activities against the lethal crucian carp hematopoietic necrosis virus. Both ligands exhibit biological activity as monomers despite the fact that the functional conformation of IFNγ is a homodimer. Both interferons have a high degree of sequence similarity, but differ in the C‐terminus region. In this region, IFNγrel 1 contains a functional nuclear localization sequence which induces the translocation of green fluorescent protein from the cytoplasm to the nucleus. IFNγrel 2 lacks this sequence. These results indicate that IFNγrel 1 and IFNγrel 2 are functional antiviral cytokines. These structurally related ligands play distinct antiviral roles through different intracellular translocation mechanisms. Thus, IFNγrels form a novel, distinct subtype included in type II IFNs. The cyprinid fish IFNγ subtype currently consists of four members, including two IFNγ isoforms and two distinct additional IFNγrel isoforms specific to the fish.
Examining weak protein–protein interactions in start codon recognition via NMR spectroscopy
Authors: Luna Rafael E. , Akabayov Sabine R. , Ziarek Joshua J. , Wagner Gerhard
Published: November 2013

Weak protein–protein interactions are critical in numerous biological processes. Unfortunately, they are difficult to characterize due to the high concentrations required for the production and detection of the complex population. The inherent sensitivity of NMR spectroscopy to the chemical environment makes it an excellent tool to tackle this problem. NMR permits the exploration of interactions over a range of affinities, yielding essential insights into dynamic biological processes. The conversion of messanger RNA to protein is one such process that requires the coordinated association of many low‐affinity proteins. During start codon recognition, eukaryotic initiation factors assemble into high‐order complexes that bind messanger RNA and bring it to the ribosome for decoding. Many of the structures of the eukaryotic initiation factors have been determined; however, little is known regarding the weak binary complexes formed and their structure‐function mechanisms. Herein, we use start codon recognition as a model system to review the relevant NMR methods for the characterization of weak interactions and the development of small molecule inhibitors.
Propensity for social interaction predicts nicotine‐reinforced behaviors in outbred rats
Authors: Wang T. , Han W. , Wang B. , Jiang Q. , Solberg‐Woods L. C. , Palmer A. A. , Chen H.
Published: November 2013

Social and genetic factors can influence smoking behavior. Using olfactogustatory stimuli as the sensory cue for intravenous nicotine self‐administration (SA), we previously showed that social learning of nicotine contingent odor cue prevented rats from developing conditioned taste aversion and allowed them to instead establish stable nicotine SA. We hypothesized that genetic factors influenced socially acquired nicotine SA. A heterogeneous stock (HS; N/NIH) of outbred rats was trained to self‐administer nicotine using the social learning protocol. Both male and female HS rats acquired nicotine SA, but females self‐administered more nicotine than males. After extinction, the context previously paired with nicotine SA, in conjunction with socially transmitted drug cues, was sufficient to cause reinstatement of drug‐seeking behavior. Wide variation in both nicotine intake and reinstatement was observed. Using multiple regression analysis, we found that measures of social interaction were significant predictors of nicotine intake and reinstatement of drug seeking in both males and females. Furthermore, measures of depression were predictors of nicotine intake in both males and females, anxiety was a predictor only in males and response to novelty was a predictor only in females. In males, measures of both depression and anxiety predicted nicotine reinstatement. Together, these data supported the ideas that genetically determined propensities for emotional and social phenotypes are significant determinants for nicotine‐reinforced behavior, and that the HS rat is a suitable tool for dissecting genetic mechanisms that may underlie the interaction between social behavior, anxiety, depression and smoking.
Genetic variation within the Chrna7 gene modulates nicotine reward‐like phenotypes in mice
Authors: Harenza J. L. , Muldoon P. P. , De Biasi M. , Damaj M. I. , Miles M. F.
Published: November 2013

Mortality from tobacco smoking remains the leading cause of preventable death in the world, yet current cessation therapies are only modestly successful, suggesting new molecular targets are needed. Genetic analysis of gene expression and behavior identified Chrna7 as potentially modulating nicotine place conditioning in the BXD panel of inbred mice. We used gene targeting and pharmacological tools to confirm the role of Chrna7 in nicotine conditioned place preference (CPP). To identify molecular events downstream of Chrna7 that may modulate nicotine preference, we performed microarray analysis of α7 knock‐out (KO) and wild‐type (WT) nucleus accumbens (NAc) tissue, followed by confirmation with quantitative polymerase chain reaction (PCR) and immunoblotting. In the BXD panel, we found a putative cis expression quantitative trait loci (eQTL) for Chrna7 in NAc that correlated inversely to nicotine CPP. We observed that gain‐of‐function α7 mice did not display nicotine preference at any dose tested, whereas conversely, α7 KO mice demonstrated nicotine place preference at a dose below that routinely required to produce preference. In B6 mice, the α7 nicotinic acetylcholine receptor (nAChR)‐selective agonist, PHA‐543613, dose‐dependently blocked nicotine CPP, which was restored using the α7 nAChR‐selective antagonist, methyllycaconitine citrate (MLA). Our genomic studies implicated a messenger RNA (mRNA) co‐expression network regulated by Chrna7 in NAc. Mice lacking Chrna7 demonstrate increased insulin signaling in the NAc, which may modulate nicotine place preference. Our studies provide novel targets for future work on development of more effective therapeutic approaches to counteract the rewarding properties of nicotine for smoking cessation.
Changes of physicochemical and sensory characteristics of packed ripe table olives from Spanish cultivars during shelf‐life
Authors: García‐García Pedro , Sánchez‐Gómez Antonio Higinio , Garrido‐Fernández Antonio
Published: November 2013

Changes in the physicochemical and sensory characteristics of commercial plain (whole) and pitted ripe olives of the Gordal, Manzanilla, Hojiblanca and Cacereña cultivars were studied during a three‐year period in conditions that mimicking the storage of such products in real life. No spoilage was developed during this period. Throughout the shelf‐life, the pH of the cover brines had a marked valley decrease at the beginning of storage followed by a progressive further decline, the surface colour (measured instrumentally) and firmness of the olives followed a first‐order kinetic decay, mitigated according to the iron and calcium contents. Also, a slight browning of the cover brines at the beginning of the storage was observed. No significant changes in most of the sensory characteristics were observed by the panel test during shelf‐life except for a limited change in olive surface colour. At the end of the shelf‐life, most of the samples were classified as ‘extra’ category according to the IOC sensory evaluation method and only plain Gordal presentation was classified as ‘first, choice or select’.
The rice OsV4 encoding a novel pentatricopeptide repeat protein is required for chloroplast development during the early leaf stage under cold stress
Authors: Gong Xiaodi , Su Qianqian , Lin Dongzhi , Jiang Quan , Xu Jianlong , Zhang Jianhui , Teng Sheng , Dong Yanjun
Published: November 2013

Pentatricopeptide repeat (PPR) proteins, characterized by tandem arrays of a 35 amino acid motif, have been suggested to play central and broad roles in modulating the expression of organelle genes in plants. However, the molecular mechanisms of most rice PPR genes remains unclear. In this paper, we isolated and characterized a temperature‐conditional virescent mutant, OsV4, in rice (Oryza sativa cultivar Jiahua1 (WT, japonica rice variety)). The mutant displays albino phenotype and abnormal chloroplasts at the three leaf stage, which gradually turns green after the four leaf stage at a low temperature (20 °C). But the mutant always develops green leaves and well‐developed chloroplasts at a high temperature (32 °C). Genetic and molecular analyses uncovered that OsV4 encodes a novel chloroplast‐targeted PPR protein including four PPR motifs. Further investigations show that the mutant phenotype is associated with changes in chlorophyll content and chloroplast development. The OsV4 transcripts only accumulate to high levels in young leaves, indicating that its expression is tissue‐specific. In addition, transcript levels of some ribosomal components and plastid‐encoded polymerase‐dependent genes are dramatically reduced in the albino mutants grown at 20 °C. These findings suggest that OsV4 plays an important role during early chloroplast development under cold stress in rice.
Internet information on xerostomia: what should patients expect?
Authors: Delli K , Livas C , Spijkervet FK , Vissink A
Published: November 2013

Objective

To assess the qualitative standards of the information distributed via the Internet regarding xerostomia.

Materials and Methods

A comprehensive electronic search was performed for ‘xerostomia’ and ‘dry mouth’ separately using four search engines. The first 30 results from each search term–engine combination were pooled for analysis. After excluding promotional product sites, discussion groups, video feeds, scientific articles, non‐operative sources, sites with denied direct access through password requirement, non‐English language domains, and online medical dictionaries, 50 Web pages were evaluated in terms of readability, accessibility, usability, and reliability using recommended research methodology the Flesch Reading Ease Score and the LIDA instrument. Author and information details were also recorded.

Results

The results revealed a variable quality of the available Internet information on xerostomia. The Web sites required advanced reading skills, while LIDA scores for accessibility, usability, and reliability ranged from medium to low with average scores extending from 29.1% to 81.3%.

Conclusions

The quality of information about xerostomia among Web sources presents high variability. The existing discrepancy should be alleviated by referring patients to evidence‐based education materials on the Internet. Improvement in xerostomia information e‐resources will contribute to a more advanced quality in oral health care.
Tannerella forsythia BspA increases the risk factors for atherosclerosis in ApoE−/− mice
Authors: Lee H‐R , Jun H‐K , Choi B‐K
Published: November 2013

Objective

The aim of this study was to evaluate the effects of Tannerella forsythia and its major surface virulence factor, BspA, on the progression of atherosclerosis in ApoE−/− mice and the expression of lipid metabolism‐related genes.

Methods

PMA‐differentiated THP‐1 cells were treated with BspA to detect foam cell formation. The proximal aortas of ApoE−/− mice injected with T. forsythia or BspA were stained with oil red O to examine lipid deposition. The serum levels of CRP, HDL, and LDL were detected by ELISA. The liver tissue of T. forsythia‐ or BspA‐injected ApoE−/− mice was examined for mRNA expression of lipid metabolism‐related genes, such as liver X receptors (LXRα and LXRβ) and ATP‐binding cassette transporter A1 (ABCA1).

Results

Tannerella forsythia and BspA induced foam cell formation in THP‐1 cells and accelerated the progression of atherosclerotic lesions in ApoE−/− mice. Mouse serum levels of CRP and LDL were increased, and HDL was decreased by T. forsythia and BspA. The expression levels of LXRα and LXRβ, and ABCA1 in liver tissue were decreased by T. forsythia and BspA.

Conclusions

Tannerella forsythia and BspA augmented atherosclerotic lesion progression in ApoE−/− mice. This process may be associated with downregulation of lipid metabolism‐related gene expression.
Red human hair pheomelanin is a potent pro‐oxidant mediating UV‐independent contributory mechanisms of melanomagenesis
Authors: Panzella Lucia , Leone Loredana , Greco Giorgia , Vitiello Giuseppe , D'Errico Gerardino , Napolitano Alessandra , d'Ischia Marco
Published: November 2013

The highest incidence of melanoma in red haired individuals is attributed to the synthesis and phototoxic properties of pheomelanin pigments. Recently, pheomelanin has also been implicated in UV‐independent pathways of oxidative stress; however, the underlying mechanisms have remained uncharted. Herein, we disclose the unprecedented property of purified red human hair pheomelanin (RHP) to promote (i) the oxygen‐dependent depletion of major cell antioxidants, for example glutathione and NADH; (ii) the autoxidative formation of melanin pigments from their precursors. RHP would thus behave as a unique ‘living’ polymer and biocatalyst that may grow by simple exposure to monomer building blocks and may trigger autoxidative processes. These results yield new clues as to the origin of the pro‐oxidant state in the red hair phenotype, uncover non‐enzymatic pathways of melanogenesis, and pave the way to innovative strategies for melanoma prevention.
MicroRNA‐206 induces G1 arrest in melanoma by inhibition of CDK4 and Cyclin D
Authors: Georgantas Robert W. , Streicher Katie , Luo Xiaobing , Greenlees Lydia , Zhu Wei , Liu Zheng , Brohawn Philip , Morehouse Christopher , Higgs Brandon W. , Richman Laura , Jallal Bahija , Yao Yihong , Ranade Koustubh
Published: November 2013

Expression profiling of microRNAs in melanoma lesional skin biopsies compared with normal donor skin biopsies, as well as melanoma cell lines compared with normal melanocytes, revealed that hsa‐miR‐206 was down‐regulated in melanoma (−75.4‐fold, P = 1.7 × 10−4). MiR‐206 has been implicated in a large number of cancers, including breast, lung, colorectal, ovarian, and prostate cancers; however, its role in tumor development remains largely unknown, its biologic function is poorly characterized, and its targets affecting cancer cells are largely unknown. MiR‐206 reduced growth and migration/invasion of multiple melanoma cell lines. Bioinformatics identified cell cycle genes CDK2, CDK4, Cyclin C, and Cyclin D1 as strong candidate targets. Western blots and 3′UTR reporter gene assays revealed that miR‐206 inhibited translation of CDK4, Cyclin D1, and Cyclin C. Additionally, hsa‐miR‐206 transfection induced G1 arrest in multiple melanoma cell lines. These observations support hsa‐miR‐206 as a tumor suppressor in melanoma and identify Cyclin C, Cyclin D1, and CDK4 as miR‐206 targets.
Description of a novel KIR3DL1*0050104 allele identified using sequence‐based techniques
Authors: Yindom L.‐M. , Wang L. , Dong T. , Rowland‐Jones S. L.
Published: November 2013

KIR3DL1*0050104 allele differs from KIR3DL1*0050101 at nucleotide positions 6709C>T (intron 5) and 11365A>G (intron 6).
Prevalence of Treponema pallidum DNA among blood donors with two different serologic tests profiles for syphilis in São Paulo, Brazil
Authors: Ferreira S. C. , de Almeida‐Neto C. , Nishiya A. S. , Di‐Lorenzo‐Oliveira C. , Ferreira J. E. , Alencar C. S. , Levi J. E. , Salles N. A. , Mendrone‐Junior A. , Sabino E. C.
Published: November 2013

The presence of Treponema pallidum DNA was assessed by real‐time PCR in samples of blood donors with reactive serologic tests for syphilis. Treponema pallidum DNA was detected in two (1·02%) of 197 samples of VDRL>8, EIA+ and FTA‐ABS+ donors, and in no sample from 80 VDRL−, EIA+ and FTA‐ABS+ donors. Donors VDRL−, EIA+ and FTA‐ABS+ lack demonstrable T. pallidum DNA in their blood and are unlike to transmit syphilis. Donors VDRL>8, EIA+ and FTA‐ABS+ carry the risk of syphilis infectivity even in concomitance to antibodies detection. Serologic screening for syphilis may still play a role to prevent its transfusion transmission.
Evaluation of 6 years of confidential unit exclusion at the Belgian Red Cross Flanders Blood Service
Authors: Vandewalle G. , Baeten M. , Bogaerts K. , Vandekerckhove P. , Compernolle V.
Published: November 2013

Background and Objectives

The effectiveness of the confidential unit exclusion (CUE) as a safety measure to the blood supply is debated. We therefore investigated the usefulness of CUE in our donor population.

Methods

Data of CUE use, donor deferrals due to different degrees of sexual or blood exposure and data of confirmed positive transfusion‐transmissible infection (TTI) markers were analyzed for the study period January 1, 2004 to December 31, 2009.

Results

The CUE user tended to be of young age, male and first time donor whereas the CUE non‐responder was more likely to be older, first time donor without a clear sex predilection. CUE had low sensitivity (0·33%) and low positive predictive value (0·02%) in detecting TTI marker positive donations. Of 46 incident cases, one donor designated his pre‐conversion donation as CUE positive. 29·6% of the donors deferred due to reported sex or intravenous drug related risk factors on the donor history questionnaire had ticked ‘I do practice risk behavior' on the CUE form. Deferrals for all sexual or blood‐blood contact related risk factors were 19·2 times higher among CUE positive donors than among CUE negative donors (95% CI, 18·5–19·9).

Conclusion

Although CUE use is associated with higher rates of TTI risk, CUE has low efficiency to detect window period donations. Moreover, misuse results in a significant loss of units. Our data indicate a low risk perception among donors, hence efforts should focus on improving donor knowledge of and on donor's responsibility to disclose TTI risk.
Pathophysiology of human heart failure: importance of skeletal muscle myopathy and reflexes
Authors: Piepoli Massimo F. , Crisafulli Antonio
Published: November 2013

New Findings

What is the topic of this review?

This article reviews the role played by reflexes arising from muscle metaboreceptors in the pathophysiology of exercise intolerance in chronic heart failure (CHF). These receptors trigger the metaboreflex, which is likely to play an important role in the genesis of exercise intolerance in CHF.

What advances does it highlight?

This article highlights that, in CHF, the target blood pressure response during muscle metaboreflex activation is achieved mainly by vasoconstriction, whereas in healthy individuals the main mechanism is an increase in cardiac output.

In the last 20 years there has been mounting evidence that chronic heart failure (CHF) has a complex pathophysiology, which begins with an abnormality of the heart as a ‘primum movens’, but involves adaptive changes in many body parts, including the cardiovascular, musculoskeletal, renal, neuroendocrine, haemostatic, immune and inflammatory systems. Alterations in skeletal muscle are also of importance in limiting functional capacity in patients with CHF, because reduced physical activity plays some part in the muscle alterations in CHF. On the whole, these abnormalities resemble those induced by physical deconditioning. Moreover, the overactivation of signals originating from skeletal muscle receptors (mechano‐metaboreceptors) is an intriguing hypothesis proposed to explain the origin of symptoms and the beneficial effect of exercise training in the CHF syndrome. These reflexes may contribute to sympathetic overactivation, to exercise intolerance and to the progression of CHF syndrome. The so‐called metaboreflex has been reported to be hyperactive in CHF and to be responsible for a paradoxical increase in systemic vascular resistance and decrease in cardiac output whenever activated in these patients. This report is a brief summary of the latest news in this area of research.
Gurson's Criterion and Its Derivation Revisited
Authors: Leblond Jean-Baptiste , Morin Léo
Published: November 2013

This paper revisits Gurson's (Gurson, A., 1975, “Plastic Flow and Fracture Behavior of Ductile Materials Incorporating Void Nucleation, Growth, and Interaction,” Ph.D. thesis, Brown University, Rhode Island; Gurson, 1977, “Continuum Theory of Ductile Rupture by Void Nucleation and Growth: Part I—Yield Criteria and Flow Rules for Porous Ductile Media,” ASME J. Eng. Mater. Technol., 99, pp. 2–15) classical limit-analysis of a hollow sphere made of some ideal-plastic von Mises material and subjected to conditions of homogeneous boundary strain rate (Mandel (Mandel, J., 1964, “Contribution Theorique a l'Etude de l'Ecrouissage et des Lois d'Ecoulement Plastique,” Proceedings of the 11th International Congress on Applied Mechanics, Springer, New York, pp. 502–509) and Hill (Hill, R., 1967, “The Essential Structure of Constitutive Laws for Metal Composites and Polycrystals,” J. Mech. Phys. Solids, 15, pp. 79–95)). Special emphasis is placed on successive approximations of the overall dissipation, based on a Taylor expansion of one term appearing in the integral defining it. Gurson considered only the approximation based on the first-order expansion, leading to his well-known homogenized criterion; higher-order approximations are considered here. The most important result is that the correction brought by the second-order approximation to the first-order one is significant for the porosity rate, if not for the overall yield criterion. This bears notable consequences upon the prediction of ductile damage under certain conditions.