bluuebunny/crossref_metadata_2025 huggingface dataset:
Adaptability to hypobaric hypoxia is facilitated through mitochondrial bioenergetics: an in vivo study
Authors: Chitra Loganathan , Boopathy Rathanam
Published: March 2013

Background and Purpose

High‐altitude pulmonary oedema (HAPE) experienced under high‐altitude conditions is attributed to mitochondrial redox distress. Hence, hypobaric hypoxia (HH)‐induced alteration in expression of mitochondrial biogenesis and dynamics genes was determined in rat lung. Further, such alteration was correlated with expression of mitochondrial DNA (mtDNA)‐encoded oxidative phosphorylation (mtOXPHOS) genes. The prophylactic effect of dexamethasone (DEX) in counteracting the HH‐induced mitochondrial distress was used as control to understand adaptation to high‐altitude exposure.

Experimental Approach

Rats pretreated with DEX were exposed to normobaric normoxia (NN) or HH. HH‐induced injury was assessed as an increase in lung water content, tissue damage and oxidant generation. Mitochondrial number, mtDNA content and mtOXPHOS activities were measured to determine mitochondrial function. The expression of mitochondrial biogenesis, dynamics and mtOXPHOS genes was studied.

Key Results

HH‐induced lung injury was associated with decreased mitochondrial number, mtDNA content and mtOXPHOS activities. HH exposure decreased the nuclear gene oestrogen‐related receptor‐α (ERRα), which interacts with PPAR‐γ coactivator‐1α (PGC‐1α) in controlling mitochondrial metabolism. Consequently, mtOXPHOS transcripts are repressed under HH. Further, HH modulated mitochondrial dynamics by decreasing mitofusin 2 (Mfn2) and augmenting fission 1 (Fis1) and dynamin‐related protein 1 (Drp1) expression. Nevertheless, DEX treatment under NN (i.e. adaptation to HH) did not affect mitochondrial biogenesis and dynamics, but increased mtOXPHOS transcripts. Further, mtOXPHOS activities increased together with reduced oxidant generation. Also, DEX pretreatment normalized ERRα along with mitochondrial dynamics genes and increased mtOXPHOS transcripts to elicit the mitochondrial function under HH.

Conclusions and Implications

HH stress (HAPE)‐mediated mitochondrial dysfunction is due to repressed ERRα and mtOXPHOS transcripts. Thus, ERRα‐mediated protection of mitochondrial bioenergetics might be the likely candidate required for lung adaptation to HH.
Rates of risk‐reducing surgery in Israeli BRCA1 and BRCA2 mutation carriers
Authors: Laitman Y , Vaisman Y , Feldman D , Helpman L , Gitly M , Paluch Shimon S , Berger R , Cohen L , Narod SA , Friedman E
Published: March 2013

The frequency of BRCA1 and BRCA2 mutations is higher in Israel than in almost all other countries. One strategy to reduce the burden of hereditary breast and ovarian cancers is to offer genetic testing followed by risk‐reducing surgery (mastectomy and salpingo‐oophorectomy) for mutation carriers. The extent to which Israeli women who carry mutations undergo these surgeries is not well characterized. Israeli women who are BRCA1 or BRCA2 mutation carriers and followed at a single high‐risk clinic were asked to complete a questionnaire detailing their clinical histories at the time of genetic results disclosure and a follow‐up questionnaire was completed 18 or more months thereafter. A total of 205 mutation carriers completed the questionnaires. Of 170 women with no cancer history, 84 (49%) had a risk‐reducing bilateral salpingo‐oophorectomy and 22 (13%) had a risk‐reducing mastectomy. Five of 35 (14.3%) women with breast cancer opted for contralateral mastectomy. Approximately one half of Israeli women with a BRCA1 or BRCA2 mutation opt for risk‐reducing oophorectomy, but the rate of risk‐reducing mastectomy is only 13%.
Chemical atopy
Authors: Puangpet Pailin , Lai‐Cheong Joey , McFadden John P.
Published: March 2013

Background. Although atopic disease is associated with protein allergy, its relationship with chemicals (haptens/contact allergens and irritants) is less clearly defined. The ‘hapten–atopy’ hypothesis, whereby significant hapten and irritant exposure during times of natural T helper (Th)2 bias (pregnancy and first year of life) promotes the development of atopy and atopic disease in the resulting child, has been previously proposed. Supporting evidence includes the practice of repeated cutaneous application of haptens in generating animal models of atopic dermatitis, and the observation of a significant increase in atopic disease in children born to mothers with occupations associated with high chemical exposure during pregnancy.

Objectives. To observe the relationship between personal chemical exposure and atopic disease in a particular case series.

Methods. We report a case series of exacerbation of atopic dermatitis after repeated cutaneous chemical exposure.

Results. Most of the patients had atopic dermatitis in young childhood that had resolved. However, after repeated chemical exposure, either occupationally as an adult or after starting to use cosmetics as a teenager, there was clear exacerbation of atopic dermatitis. Patch tests gave negative results in most cases.

Conclusions. We propose that repeated exposure to chemicals in patients with an atopic background can occasionally lead to reactivation of atopic dermatitis.
Penetration and haptenation of p‐phenylenediamine
Authors: Pot Laura M. , Scheitza Simone M. , Coenraads Pieter‐Jan , Blömeke Brunhilde
Published: March 2013

Although p‐phenylenediamine (PPD) has been recognized as an extreme sensitizer for many years, the exact mechanism of sensitization has not been elucidated yet. Penetration and the ability to bind to proteins are the first two hurdles that an allergen has to overcome to be able to sensitize. This review is an overview of studies regarding PPD penetration through skin (analogues) and studies on the amino acids that are targeted by PPD. To complete this review, the auto‐oxidation and N‐acetylation steps involved in PPD metabolism are described. In summary, under normal hair dyeing exposure conditions, <1% of the applied PPD dose penetrates the skin. The majority (>80%) of PPD that penetrates will be converted into the detoxification products monoacetyl‐PPD and diacetyl‐PPD by the N‐acetyltransferase enzymes. The small amount of PPD that does not become N‐acetylated is susceptible to auto‐oxidation reactions, yielding protein‐reactive PPD derivatives. These derivatives may bind to specific amino acids, and some of the formed adducts might be the complexes responsible for sensitization. However, true in vivo evidence is lacking, and further research to unravel the definite mechanism of sensitization is needed.
Finding the optimal patch test material and test concentration to detect contact allergy to geraniol
Authors: Hagvall Lina , Karlberg Ann‐Therese , Christensson Johanna B.
Published: March 2013

Background. Geraniol is a commonly used fragrance terpene, and is tested in the baseline series in fragrance mix I. Geraniol is a pro‐hapten and a pre‐hapten, and sensitizers are formed in the autoxidation and skin metabolism of geraniol. Previous patch testing with air‐exposed (oxidized) geraniol has suggested that oxidized geraniol could be a better marker for contact allergy to geraniol than pure geraniol.

Objectives. To find the optimal patch test substance and concentration for detecting contact allergy to geraniol.

Patients and methods. Six hundred and fifty‐five patients were patch tested with pure and oxidized geraniol at 4.0%, 6.0% and 11.0% in petrolatum. Before patch testing, the irritant properties of pure and oxidized geraniol were studied in 27 patients at 2.5%, 5.0%, 10.0% and 20.0% pet.

Results. Pure geraniol detected positive reactions in 0.15–1.1% of the patients, and oxidized geraniol detected positive reactions in 0.92–4.6% of the patients. Reactions to pure geraniol in patients not reacting to oxidized geraniol indicated metabolic activation of geraniol. Neither pure nor oxidized geraniol gave significant irritant reactions.

Conclusions. Increasing the test concentrations of pure and oxidized geraniol enables the detection of more cases of contact allergy. Oxidized geraniol detects more patients than pure geraniol, but patch testing with only oxidized geraniol does not detect all cases of contact allergy to geraniol.
An international multicentre study on the allergenic activity of air‐oxidized R‐limonene
Authors: Bråred Christensson Johanna , Andersen Klaus E. , Bruze Magnus , Johansen Jeanne D. , Garcia‐Bravo Begoña , Giménez‐Arnau Ana , Goh Chee‐Leok , Nixon Rosemary , White Ian R.
Published: March 2013

Background. Limonene is a common fragrance terpene that, in its pure form, is not allergenic or is a very weak allergen. However, limonene autoxidizes on air exposure, and the oxidation products can cause contact allergy. Oxidized R‐limonene has previously been patch tested in multicentre studies, giving 2–3% positive patch test reactions in consecutive patients.

Objectives. To investigate whether oxidized R‐limonene 3.0% in petrolatum, with a stable concentration of the main haptens, limonene hydroperoxides (Lim‐OOHs), could be a useful tool for the detection of contact allergy in an international setting.

Methods. Oxidized R‐limonene 3.0% (Lim‐OOHs 0.33%) pet. was tested in 2900 consecutive dermatitis patients in Denmark, the United Kingdom, Singapore, Spain, Sweden, and Australia.

Results. Overall, 5.2% (range 2.3–12.1%) of the patients showed a positive patch test reaction to oxidized R‐limonene. Doubtful reactions were found in 7.0% of the patients (range 0–24%). Few irritant reactions were seen.

Conclusions. Oxidized R‐limonene at 3.0% pet. with a specified content of Lim‐OOHs 0.33% is a standardized and useful tool for the detection of contact allergy in dermatitis patients. Many patients showing positive patch test reactions to oxidized R‐limonene would not be informed of their fragrance allergy if this specific test had not been performed.
Photopatch testing: recommendations for a European photopatch test baseline series
Authors: Gonçalo Margarida , Ferguson James , Bonevalle Annie , Bruynzeel Derk P , Giménez‐Arnau Ana , Goossens An , Kerr Alastair , Lecha Mario , Neumann Norbert , Niklasson Bo , Pigatto Paolo , Rhodes Lesley E. , Rustemeyer Thomas , Sarkany Robert , Thomas Pierre , Wilkinson Mark
Published: March 2013

In order to establish a consensus recommendation for performing photopatch testing, a photopatch test taskforce group was established under the joint umbrella of the European Society for Contact Dermatitis and the European Society for Photodermatology in 2000. After proposing the most adequate methodology in 2004 and completing a European multicentre photopatch test study in 2011, this taskforce is recommending a list of photoallergens that should form part of a baseline series for photopatch testing in Europe. It contains mainly ultraviolet filters and drugs, mostly non‐steroidal anti‐inflammatory drugs. The choice of chemicals was based on the results of a recent multicentre study, previous published cases of photoallergy, and use of the substances in the European market.

It is suggested that an extended list of photoallergens should be photopatch tested in selected cases, along with patients' own products. Two contact allergens, cinnamyl alcohol and decyl glucoside, should be simultaneously patch tested in order to clarify photopatch and patch test reactions, respectively, to ketoprofen and methylene bis‐benzotriazolyl tetramethylbutylphenol (Tinosorb M™).
FEATURE SELECTION BASED ON COMPACTNESS AND SEPARABILITY: COMPARISON WITH FILTER‐BASED METHODS
Authors: Chen Chien‐Hsing
Published: March 2013

Selecting a subset of salient features for performing clustering using a clustering learning algorithm has been explored extensively in many real‐world applications. To select salient features during training, the filter model evaluates the intrinsic characteristics of each individual feature but is not permitted to use a clustering learning algorithm that provides clustered information to train the features. In particular, the filter model aims to predict unobservable clusters and measure how the features help provide satisfactory within‐cluster and between‐cluster scatters to achieve a good clustering quality. However, it is generally difficult to achieve both scatters in the filter model. For example, a random variable with a large variance may raise only the between‐cluster scatter, whereas another variable following a uniform distribution may raise only the within‐cluster scatter. In this paper, we present a new filter‐based method to quantify features that consider feature compactness and separability to ensure that both scatters are raised. Moreover, our method adopts a new search strategy to locate the best feature salience vector instead of visiting the space of all the possible feature subsets. After the benchmark data sets are tested, the experimental results indicate that our method performs better than many benchmark filter‐based methods at selecting a feature subset to perform clustering.
Does functional type vulnerability to multiple threats depend on spatial context in Mediterranean‐climate regions?
Authors: Syphard Alexandra D. , Regan Helen M. , Franklin Janet , Swab Rebecca M. , Bonebrake Timothy C.
Published: March 2013

Aim

Conservation efforts in Mediterranean‐climate regions are complicated by species' variability in response to multiple threats. Functional type classifications incorporating life history traits with disturbance response strategies provide a framework for predicting groups of species' response to fire, but it is unclear whether these classifications will be useful when species are exposed to multiple threats or differ in spatial context. We evaluate whether species of the same fire‐response functional type exhibit similar responses to disturbance relative to, and in combination with, climate and land‐use change and whether the dominant threat depends on spatial context.

Location

Mediterranean southern California.

Methods

We developed species distribution models under current and future climate conditions for two fire‐obligate seeding native shrub species that differ in geographical location and area of occupancy. Dynamic habitat maps representing alternative scenarios of climate change and urban growth were coupled with population models and simulated stochastic fire regimes.

Results

The disturbance that defines their classification, fire, is projected to be the most serious threat to both species when fire frequency is high. At longer fire return intervals, however, the projected ranking of threats differed between the species, and spatial context played an important role in defining vulnerability.

Main conclusions

Considering ongoing increases in fire frequency in Mediterranean‐climate regions worldwide, functional type classification based on disturbance response may continue to provide a useful framework for biodiversity conservation efforts, but spatial context should also be accounted for. It may be most useful to consider the distribution of vulnerable species with regard to urban development patterns, areas of ‘high‐velocity’ climate shifts, and places where altered fire regimes are likely to interact with other threats.
High single‐session success rate of endoscopic bilateral stent‐in‐stent placement with modified large cell Niti‐S stents for malignant hilar biliary obstruction
Authors: Kogure Hirofumi , Isayama Hiroyuki , Nakai Yousuke , Tsujino Takeshi , Matsubara Saburo , Yashima Yoko , Ito Yukiko , Hamada Tsuyoshi , Takahara Naminatsu , Miyabayashi Koji , Mizuno Suguru , Mohri Dai , Kawakubo Kazumichi , Sasaki Takashi , Yamamoto Natsuyo , Hirano Kenji , Sasahira Naoki , Tada Minoru , Koike Kazuhiko
Published: March 2013

Background

Endoscopic bilateral self‐expandable metallic stent (SEMS) placement in a stent‐in‐stent method for malignant hilar biliary obstruction is technically challenging. Technical difficulties in the initial placement and reinterventions for stent occlusion are disadvantages inherent to this stent‐in‐stent method. We previously reported the feasibility of Niti‐S large cell D‐type biliary stents (LCD). This multicenter prospective consecutive study evaluated the efficacy of bilateral SEMS placement using modified LCD with large and uniform cells, a slimmer delivery system and high radial force.

Patients and Methods

From July 2010 to June 2011, 26 consecutive patients with unresectable malignant hilar biliary obstruction underwent endoscopic bilateral placement of modified LCD in a stent‐in‐stent method at three tertiary hospitals. Ten patients had gallbladder cancer, eight had cholangiocarcinoma, four had lymph node metastasis, two had intrahepatic cholangiocarcinoma, and two had liver metastasis.

Results

Single‐session and final technical success rate was 96% and 100%, respectively. Functional success rate was 89%. Stent occlusion occurred in 11 patients (42%) because of sludge (n = 7) or tumor ingrowth (n = 4). Endoscopic bilateral reintervention was technically easy and successful: six patients had stent clearance by balloon sweeping and five had plastic stent placement. According to Kaplan–Meier analysis, median survival and stent patency were 220 days and 157 days, respectively.

Conclusions

Modified LCD achieved a high technical success rate both in the initial stent‐in‐stent placement and in bilateral reinterventions in patients with malignant hilar biliary obstruction.
Biliary sphincterotomy is not required for bile duct stent placement
Authors: Wilcox C. Mel , Kim Hwasoon , Ramesh Jayapal , Trevino Jessica , Varadarajulu Shyam
Published: March 2013

Background

The aim of the present study was to assess the success and outcome of bile duct stent placement without the use of endoscopic biliary sphincterotomy (EBS).

Patients and Methods

Over a period of 10 years and 9 months, all patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) were prospectively identified. Bile duct stent placement was routinely done without EBS unless additional therapy (stone removal, multiple stenting) was anticipated.

Results

Of 5020 patients who underwent ERCP, bile duct stents were placed in 1668 patients. After excluding those requiring additional endoscopic therapy, 1112 patients (89.5%) had ERCP and stent placement without a sphincterotomy and 130 patients (10.5%) had ERCP and stent placement with asphincterotomy. Deployed endoprostheses were self‐expandable metallic stents in 15.7% and plastic in 77.5%. Caliber of plastic stents was 10 Fr in 78.9% and <10 Fr in 21.1%. All stents were successfully placed in these 1112 patients without the need for EBS. Comparing patients undergoing bile duct stenting with and without sphincterotomy, no difference was seen in rates of pancreatitis (1.54% vs 2.07%, P > 0.9999).

Conclusion

Single bile duct stents, both plastic and metal, can be deployed without EBS.
Activated complement factor 3 is associated with liver fat and liver enzymes: the CODAM study
Authors: Wlazlo Nick , van Greevenbroek Marleen M. J. , Ferreira Isabel , Jansen Eugene H. J. M. , Feskens Edith J. M. , van der Kallen Carla J. H. , Schalkwijk Casper G. , Bravenboer Bert , Stehouwer Coen D. A.
Published: March 2013

Background

The complement system may be involved in the pathogenesis of alcoholic and nonalcoholic liver disease, although studies in humans are scarce. For this reason, we investigated whether circulating levels of activated complement factor 3 (C3a) were associated with hepatic steatosis and hepatocellular damage.

Materials and methods

Plasma C3a, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma‐glutamyl transferase (GGT) were determined in 523 individuals (61% men, age 59 ± 7 years). Liver enzymes (LEs) were standardized and compiled into a LE score. Liver fat content was estimated using a predictive equation that has recently been validated with magnetic resonance spectrometry. Cross‐sectional associations between C3a and liver fat or LE s were investigated with multiple linear regression analyses, stratified in no‐to‐moderate vs. heavy alcohol consumers (men: > 30 g/day; women: > 20 g/day).

Results

C3a was associated with liver fat percentage both in the no‐to‐moderate (β = 0·223; 95%CI 0·036; 0·409) and in the heavy alcohol consumers (β = 0·632; 95%CI 0·259–1·004; P‐interaction = 0·047). C3a was also associated with the LE score in heavy alcohol consumers (β = 0·917; 95%CI 0·443–1·392), but not in no‐to‐moderate alcohol consumers (β = 0·042; 95%CI −0·198 to 0·281; P‐interaction = 0·001).

Conclusions

C3a levels, as a marker of complement activation, were associated with liver fat content and hepatocellular injury, at least in subjects who consume considerable amounts of alcohol daily.
Differences in ecomorphology and microhabitat use of four saproxylic larvae (Diptera, Syrphidae) inScots pine stump rot holes
Authors: ROTHERAY ELLEN L.
Published: March 2013

Co‐existence and microhabitat partitioning was explored in larvae of four species of hoverfly which occupy rot holes in Scots Pine Pinus sylvestris L. in Scotland, U.K. including the endangered pine hoverfly Blera fallax (Linnaeus), and three more common species, Callicera rufa (Schummel), Myathropa florea (Linnaeus), and Sphegina clunipes (Fallén) (Diptera, Syrphidae). The primary aim of the study was to investigate competitive exclusion risks to B. fallax, a species that now remains at just one site in the U.K.

Morphological differences were examined between species and these were compared with microhabitat use in an artificial rot hole. In addition, larval growth was measured for three of the species in different volumes of pinewood substrate to investigate differences in development in response to varying substrate levels.

Field surveys confirmed that B. fallax, C. rufa, and M. florea frequently co‐occur in pine rot holes. Species differed in their growth rates and responses to variation in substrate level. Blera fallax developed quickly before winter, and decreasing substrate volume significantly inhibited growth, whereas C. rufa and M. florea took 6 months longer to achieve a critical size for eclosion.

Each species inhabited a distinct depth in the rot hole and exhibited correspondingly different behaviours associated with respiration and the length of their posterior breathing tubes.

The microhabitat partitioning observed in this study may facilitate the coexistence of these four species, and suggests that competitive exclusion will not hamper conservation management efforts for B. fallax.
Biodiversity of stream insects in the Malaysian Peninsula: spatial patterns and environmental constraints
Authors: ABDO AL‐SHAMI SALMAN , MD RAWI CHE SALMAH , AHMAD ABU HASSAN , ROSMAHANIE MADRUS MADZIATUL
Published: March 2013

The spatial variation in Ephemeroptera, Plecoptera, and Trichoptera (EPT) taxonomic composition in headwater forested streams of peninsular Malaysia was studied. Several environmental parameters were assessed for their importance in regulating the composition of assemblages across the spatial extent of the Malaysian bioregion. The spatial variables were expressed as vectors based on principal coordinates of neighbour matrices (PCNM). The forward selection based on two stopping criteria was used to identify the key environmental and spatial variables controlling the EPT taxonomic composition.

Eigenvector‐based spatial filtering was employed to investigate spatial patterns in EPT composition, and the variation partitioning technique was used to determine the relative importance of environmental and spatial factors in application on EPT composition. The forward selection retained five parameters [altitude, biochemical oxygen demand (BOD), water velocity, ammonia, and dissolved oxygen (DO)] which explained 13.2% of the total variance in EPT composition. The three selected spatial variables (PCNM vectors) accounted for 8.4% of the composition variation. However, the spatially‐structured environmental variables explained 7.5% of the total variance in EPT composition. The variation in altitude correlated with broad‐scale spatial extent and was the most important factor regulating the EPT composition in peninsular Malaysia.

Our study revealed spatially‐structured patterns in the EPT composition, showing a richness decrease from the south to the north of peninsular Malaysia.
Stable bottom‐up processing during dynamic top‐down modulations in monkey auditory cortex
Authors: Massoudi Roohollah , Van Wanrooij Marc M. , Van Wetter Sigrid M. C. I. , Versnel Huib , Van Opstal A. John
Published: March 2013

It is unclear whether top‐down processing in the auditory cortex (AC) interferes with its bottom‐up analysis of sound. Recent studies indicated non‐acoustic modulations of AC responses, and that attention changes a neuron's spectrotemporal tuning. As a result, the AC would seem ill‐suited to represent a stable acoustic environment, which is deemed crucial for auditory perception. To assess whether top‐down signals influence acoustic tuning in tasks without directed attention, we compared monkey single‐unit AC responses to dynamic spectrotemporal sounds under different behavioral conditions. Recordings were mostly made from neurons located in primary fields (primary AC and area R of the AC) that were well tuned to pure tones, with short onset latencies. We demonstrated that responses in the AC were substantially modulated during an auditory detection task and that these modulations were systematically related to top‐down processes. Importantly, despite these significant modulations, the spectrotemporal receptive fields of all neurons remained remarkably stable. Our results suggest multiplexed encoding of bottom‐up acoustic and top‐down task‐related signals at single AC neurons. This mechanism preserves a stable representation of the acoustic environment despite strong non‐acoustic modulations.
Social isolation perturbs experience‐driven synaptic glutamate receptor subunit 4 delivery in the developing rat barrel cortex
Authors: Miyazaki Tomoyuki , Kunii Misako , Jitsuki Susumu , Sano Akane , Kuroiwa Yoshiyuki , Takahashi Takuya
Published: March 2013

In neonates, the stress of social isolation can alter developing neural circuits and cause mental illness. However, the molecular and cellular bases for these effects are poorly understood. Experience‐driven synaptic AMPA receptor delivery is crucial for circuit organisation during development. In the rat, whisker experience drives the delivery of glutamate receptor subunit 4 (GluA4) but not glutamate receptor subunit 1 (GluA1) to layer 4–2/3 pyramidal synapses in the barrel cortex during postnatal day (P)8–10, whereas GluA1 but not GluA4 is delivered to these synapses during P12–14. We recently reported that early social isolation disrupts experience‐driven GluA1 delivery to layer 4–2/3 pyramidal synapses during P12–14. Here, we report that neonatal isolation affects even earlier stages of development by preventing experience‐dependent synaptic GluA4 delivery. Thus, social isolation severely affects synaptic maturation throughout early postnatal development.
Prefrontal cortical–striatal dopamine receptor mRNA expression predicts distinct forms of impulsivity
Authors: Simon Nicholas W. , Beas Blanca S. , Montgomery Karienn S. , Haberman Rebecca P. , Bizon Jennifer L. , Setlow Barry
Published: March 2013

Variation in dopamine receptor levels has been associated with different facets of impulsivity. To further delineate the neural substrates underlying impulsive action (inability to withhold a prepotent motor response) and impulsive choice (delay aversion), we characterised rats in the Differential Reinforcement of Low Rates of Responding task and a delay discounting task. We also measured performance on an effort‐based discounting task. We then assessed D1 and D2 dopamine receptor mRNA expression in subregions of the prefrontal cortex and nucleus accumbens using in situ hybridisation, and compared these data with behavioral performance. Expression of D1 and D2 receptor mRNA in distinct brain regions was predictive of impulsive action. A dissociation within the nucleus accumbens was observed between subregions and receptor subtypes; higher D1 mRNA expression in the shell predicted greater impulsive action, whereas lower D2 mRNA expression in the core predicted greater impulsive action. We also observed a negative correlation between impulsive action and D2 mRNA expression in the prelimbic cortex. Interestingly, a similar relationship was present between impulsive choice and prelimbic cortex D2 mRNA, despite the fact that behavioral indices of impulsive action and impulsive choice were uncorrelated. Finally, we found that both high D1 mRNA expression in the insular cortex and low D2 mRNA expression in the infralimbic cortex were associated with willingness to exert effort for rewards. Notably, dopamine receptor mRNA in these regions was not associated with either facet of impulsivity. The data presented here provide novel molecular and neuroanatomical distinctions between different forms of impulsivity, as well as effort‐based decision‐making.
The Responses of Duetting Antbirds to Stereo Duet Playback Provide Support for the Joint Territory Defence Hypothesis
Authors: Koloff Julianne , Mennill Daniel J.
Published: March 2013

In multiple animal taxa, including many birds and primates, members of mated pairs produce coordinated acoustic displays known as duets. By observing the behaviour of territorial animals as they respond to playback‐simulated duets of rivals, we can gain insight into the behavioural significance of vocal duets. Playback experiments, however, have been conducted across a very narrow range of duetting animals. Furthermore, many studies have been conducted with single‐speaker playback, whereas stereo‐speaker playback offers more spatially realistic simulation of duets. Moreover, by evaluating the reactions of animals to separate loudspeakers broadcasting male and female duet contributions, we can study the interactions of both males and females with same‐sex vs. opposite‐sex rivals. We used a paired experimental design to broadcast duet stimuli through a single‐speaker and a stereo‐speaker apparatus to 30 pairs of duetting barred antshrikes Thamnophilus doliatus in Costa Rica. Our goals were (1) to evaluate whether territorial antbirds respond more aggressively to male vs. female duet components and (2) to assess aggressive responses of antbirds towards single‐speaker vs. stereo‐speaker playback. Neither males nor females differentiated between the loudspeaker simulating the male vs. female duet contribution during stereo‐speaker playback trials. Barred antshrikes displayed significantly stronger responses to stereo‐speaker playback compared with single‐speaker playback. Males displayed stronger playback responses than females with closer, quicker and more vocal responses. These results provide evidence for a joint resource defence function of antbird duets given that pairs responded together with equivalent intensity to male and female simulated intruders. This is the first study to show that although duetting is an aggressive territorial signal, birds do not necessarily respond to sex‐specific components of duets. Our results support the idea that spatially realistic stereo presentation of duet stimuli is critical for experimental duet research.
Carnosic acid, a phenolic diterpene from rosemary, prevents UV‐induced expression of matrix metalloproteinases in human skin fibroblasts and keratinocytes
Authors: Park Miyoung , Han Jiwon , Lee Chang Seok , Heung Soo Baek , Lim Kyung‐Min , Ha Hunjoo
Published: March 2013

Exposure of the skin to ultraviolet (UV) irradiation induces photoageing through the up‐regulation of matrix metalloproteinases (MMPs) and subsequent breakdown of extracellular matrices. Reactive oxygen species (ROS) and epidermal growth factor receptor (EGFR) activation play central roles in UV‐induced MMP expression through initiating extracellular signal‐regulated kinase (ERK)–mediated AP‐1 signalling. We aimed to explore the effects of carnosic acid (CA), a phenolic diterpene from rosemary, on UV‐induced MMP expression in human skin cells. Molecular mechanism underlying the effects of CA was also examined in the aspect of MMP expression, ERK/AP‐1 pathway, ROS generation and EGFR activation. Human dermal fibroblast cell line (Hs68), primary normal human dermal fibroblasts (HDFs) and normal human epidermal keratinocytes (HEKs) were employed, and antiphotoageing effects of CA were assessed by Western blotting, quantitative real‐time PCR and enzyme assays. CA significantly inhibited UVA‐ and UVB‐induced expression of MMP‐1, MMP‐3 and MMP‐9 in a concentration‐dependent manner in Hs68 cells. UVB‐induced ERK activation and the formation of transcription factor, AP‐1, were significantly suppressed by CA. Among the upstream events of MMP expression, UVB‐induced ROS generation was attenuated by CA, while EGFR activation was not affected. Confirming the antiphotoageing effects of CA through the suppression of UV‐induced ROS generation, UVB‐enhanced GADD45 expression, a marker for oxidative DNA damages was significantly reduced by CA. Inhibitory effects of CA on UVB‐induced MMP expression could be also seen in HDFs and HEKs. Collectively, our study demonstrates that CA inhibits the UV‐enhanced MMPs in human skin cells through the inhibition of ROS and the suppression of ERK/AP‐1 activation.
OPPIDUM surveillance program: 20 years of information on drug abuse in France
Authors: Frauger Elisabeth , Moracchini Christophe , Le Boisselier Reynald , Braunstein David , Thirion Xavier , Micallef Joëlle
Published: March 2013

It is important to assess drug abuse liability in ‘real life’ using different surveillance systems. Some are based on specific population surveys, such as individuals with drug abuse or dependence, or under opiate maintenance treatment, because this population is very familiar with drugs and is more likely to divert or abuse them. In France, an original surveillance system based on this specific population and called ‘Observation of illegal drugs and misuse of psychotropic medications (OPPIDUM) survey’ was set up in 1990 as the first of its kind. The aim of this article is to describe this precursor of French drug abuse surveillance using different examples, to demonstrate its ability to effectively give health authorities and physicians interesting data on drug abuse. OPPIDUM is an annual, cross‐sectional survey that anonymously collects information on abuse and dependence observed in patients recruited in specialized care centers dedicated to drug dependence. From 1990 to 2010, a total of 50 734 patients were included with descriptions of 102 631 psychoactive substance consumptions. These data have outlined emergent behaviors such as the misuse of buprenorphine by intravenous or nasal administration. It has contributed to assess abuse liability of emergent drugs such as clonazepam or methylphenidate. This surveillance system was also able to detect the decrease of flunitrazepam abuse following implementation of regulatory measures. OPPIDUM's twenty years of experience clearly demonstrate that collection of valid and useful data on drug abuse is possible and can provide helpful information for physicians and health authorities.
Regulatable transgenic mouse models of Alzheimer disease: onset, reversibility and spreading of Tau pathology
Authors: Hochgräfe Katja , Sydow Astrid , Mandelkow Eva‐Maria
Published: March 2013

Accumulation of amyloidogenic proteins such as Tau is a hallmark of neurodegenerative diseases including Alzheimer disease and fronto‐temporal dementias. To link Tau pathology to cognitive impairments and defects in synaptic plasticity, we created four inducible Tau transgenic mouse models with expression of pro‐ and anti‐aggregant variants of either full‐length human Tau (hTau40/ΔK280 and hTau40/ΔK280/PP) or the truncated Tau repeat domain (TauRD/ΔK280 and TauRD/ΔK280/PP). Here we review the histopathological features caused by pro‐aggregant Tau, and correlate them with behavioral deficits and impairments in synaptic transmission. Both pro‐aggregant Tau variants cause Alzheimer‐like features, including synapse loss, mis‐localization of Tau into the somatodendritic compartment, conformational changes and hyperphosphorylation. However, there is a clear difference in the extent of Tau aggregation and neurotoxicity. While pro‐aggregant full‐length hTau40/ΔK280 leads to a ‘pre‐tangle’ pathology, the repeat domain TauRD/ΔK280 causes massive formation of neurofibrillary tangles and neuronal loss in the hippocampus. However, both Tau variants cause co‐aggregation of human and mouse Tau and similar functional impairments. Thus, earlier Tau pathological stages and not necessarily neurofibrillary tangles are critical for the development of cognitive malfunctions. Most importantly, memory and synapses recover after switching off expression of pro‐aggregant Tau. The rescue of functional impairments correlates with the rescue of most Tau pathological changes and most strikingly the recovery of synapses. This implies that tauopathies as such are reversible, provided that amyloidogenic Tau is removed. Therefore, our Tau transgenic mice may serve as model systems for in vivo validation of therapeutic strategies and drug candidates with regard to cognition and synaptic function.
Identification of small subunit of serine palmitoyltransferase a as a lysophosphatidylinositol acyltransferase 1‐interacting protein
Authors: Hirata Yusuke , Yamamori Natsumi , Kono Nozomu , Lee Hyeon‐Cheol , Inoue Takao , Arai Hiroyuki
Published: March 2013

Lysophosphatidylinositol acyltransferase 1 (LPIAT1), also known as MBOAT7, is a phospholipid acyltransferase that selectively incorporates arachidonic acid (AA) into the sn‐2 position of phosphatidylinositol (PI). We previously demonstrated that LPIAT1 regulates AA content in PI and plays a crucial role in brain development in mice. However, how LPIAT1 is regulated and which proteins function cooperatively with LPIAT1 are unknown. In this study, using a split‐ubiquitin membrane yeast two‐hybrid system, we identified the small subunit of serine palmitoyltransferase a (ssSPTa) as an LPIAT1‐interacting protein. ssSPTa co‐immunoprecipitated and colocalized with LPIAT1 in cultured mammalian cells. Knockdown of ssSPTa decreased the LPIAT1‐dependent incorporation of exogenous AA into PI but did not affect the in vitro enzyme activity of LPIAT1 in the microsomal fraction. Interestingly, knockdown of ssSPTa decreased the protein level of LPIAT1 in the crude mitochondrial fraction but not in total homogenate or the microsomal fraction. LPIAT1 was localized to the mitochondria‐associated membrane (MAM), where AA‐selective acyl‐CoA synthetase is enriched. These results suggest that ssSPTa plays a role in fatty acid remodeling of PI, probably by facilitating the MAM localization of LPIAT1.
Immune tolerance induction in haemophilia A patients with inhibitors by treatment with recombinant factor VIII: a retrospective non‐interventional study
Authors: Rivard G. E. , Rothschild C. , Toll T. , Achilles K.
Published: March 2013

Immune tolerance induction (ITI) can overcome inhibitory factor VIII (FVIII) antibodies in haemophilia A patients receiving FVIII replacement therapy. The objective was to evaluate the use of sucrose‐formulated, full‐length recombinant FVIII (rFVIII‐FS) for ITI therapy. Patients (<8 years at ITI start) with severe haemophilia A and a peak inhibitor titre >5 Bethesda units (BU) who underwent ITI with any rFVIII‐FS dose for ≥9 months (or until success) were eligible for this retrospective study. Efficacy analyses included descriptions of ITI treatment regimens and outcomes; ITI success was determined solely at the discretion of the investigator. Safety analyses included assessment of adverse events. Of 51 enrolled patients, 32 [high dose (≥85 IU kg−1 day−1), n = 21; low dose, n = 11] were eligible for analysis. ITI was successful in 69% (22/32) of patients (high dose, 66.7%; low dose, 72.7%) after a median of 1.4 years (range, 0.1–3.6 years). Influencing factors for ITI success were start of ITI <1 year after inhibitor detection and an inhibitor titre <10 BU at ITI start. All patients successfully tolerized with ITI continued to receive rFVIII‐FS prophylaxis as maintenance therapy, with no inhibitor recurrence from the end of ITI until study enrolment. Use of rFVIII‐FS for ITI was effective and well tolerated; success rates were similar to those in published studies.
Protected by nature? Effects of strenuous physical exercise on FVIII activity in moderate and mild haemophilia A patients: a pilot study
Authors: Groen W. G. , den Uijl I. E. M. , van der Net J. , Grobbee D. E. , de Groot Ph. G. , Fischer K.
Published: March 2013

Increase of factor VIII activity (FVIII) after physical exercise has been reported in healthy subjects and small‐scale studies in patients with coagulopathies. The aim was to study whether moderate and mild haemophilia A patients are able to increase their endogenous FVIII activity levels by physical activity. We studied changes in FVIII activity levels after high‐intensity exercise in 15 haemophilia A patients, 20–39 years, eight with moderate, seven with mild haemophilia. Patients cycled until volitional exhaustion, blood samples were drawn before and 10 min after the exercise test. FVIII activity increased 2.5 times (range 1.8–7.0 times), for both severities. Absolute increases were markedly different: median 7 IU dL−1 (range 3–9 IU dL−1) in patients with moderate, compared to 15 IU dL−1 (range 6–62 IU dL−1) in mild haemophilia patients. VWF and VWFpp increased independently of severity; median 50% (range 8–123%) and median 165% (range 48–350%), respectively, reflecting acute release of VWF. These observations may be used to promote high‐intensity activities before participating in sports for moderate and mild haemophilia A patients, to reduce bleeding risk. Further studies are warranted to fully appreciate the clinical significance of exercise on different levels of intensity in patients with mild and moderate haemophilia A.
El talón de Aquiles del proyecto de producción en serie aplicado a los servicios en la administración de la seguridad social: el caso del Crédito Universal en el Reino Unido
Authors: Seddon John , O'Donovan Brendan
Published: March 2013

El presente artículo ofrece una visión crítica de las reformas del Gobierno del Reino Unido relativas a las prestaciones previstas en el marco del denominado Crédito Universal. Se dice que el Crédito Universal está destinado a fracasar a causa de la política que especifica el modo de prestar estos servicios (digitalizados por omisión). Los autores afirman que se ha permitido que el concepto de producción en serie se infiltre de manera discreta pero ubicua en la gestión de los medios por los que el Gobierno pretende conseguir el objetivo de la política de valorización del trabajo. Siguiendo el método Vanguard de Seddon, se analiza un ejemplo práctico de cómo unas autoridades locales concibieron un mejor servicio de los subsidios a la vivienda. Los resultados de este servicio incluyen la posibilidad de tratar un 50 por ciento más de solicitudes con menos recursos en la mitad del plazo oficial. Por último, el artículo destaca la necesidad de desarrollar una política mayormente basada en pruebas.
Brechas en la protección social de la salud y en los cuidados de larga duración en Europa: ¿bancarrota para la tercera edad?
Authors: Scheil‐Adlung Xenia , Bonan Jacopo
Published: March 2013

Si bien durante muchos años los países europeos han supervisado el gasto público en prestaciones de salud y cuidados de larga duración, se ha conferido menor atención a las consecuencias financieras que representan los pagos directos personales para las personas mayores que necesitan acceder a dichas prestaciones de cuidado. A través del análisis de los datos transversales procedentes de la Encuesta de Salud, Envejecimiento y Jubilación en Europa (SHARE, por sus siglas en inglés), representativos de la población anciana de once países europeos, descubrimos que en los países europeos es muy común que las personas mayores abonen por cuenta propia las prestaciones de salud y los cuidados de larga duración. Estos gastos directos se repercuten de modo significativo en la renta disponible: el 95 por ciento de las personas mayores abonan de modo directo prestaciones médicas y el 5 por ciento de ellas, los cuidados de larga duración. Estos desembolsos provocan una disminución de los ingresos de entre el 5 y el 10 por ciento. El 0,7 por ciento de los hogares con personas mayores que recurren a prestaciones médicas y el 0,5 por ciento de los hogares con personas mayores que reciben cuidados de larga duración caen en la ruina financiera a raíz del exceso de pagos directos. Los más afectados son los pobres, las mujeres y los muy ancianos.
AMERICA'S DEBT SAFETY‐NET
Authors: MONTGOMERIE JOHNNA
Published: March 2013

This article evaluates the rapid escalation of American household debt in relation to the changing dynamics of liberal welfare capitalism. Starting with the outcome of rising household debt levels during the credit and asset bubble of 2001–7 it argues that the failure of asset‐based welfare and the inability of households to move beyond their historical dependence on earned income made indebtedness essential to household social participation and protection. It examines the unique relationship of young adults (households headed by persons under age 35) and senior citizens (households headed by persons over age 65) to the liberal welfare regime, in particular the ways in which these relationships were shaped by the 2001–7 credit and asset bubble. By using a framework in which debt is analyzed as a claim against income, alongside other costs of social participation and daily living, we see the impact of the credit and asset boom on both young adults and senior citizens: growing indebtedness and financial insecurity.
Global health risks and cosmopolitisation: from emergence to interference
Authors: Figuié Muriel
Published: March 2013

According to Beck’s ‘World at Risk’ theory, global risks push nations towards a cosmopolitisation of their health policy and open opportunities for a democratic turn. This article provides an empirical analysis of Beck’s theory, based on the experience of Vietnamese authorities from 2003 to 2007 in managing the emerging avian flu virus. It shows how Vietnam’s framing of avian flu has shifted, under the pressure from international organisations and the US administration, from an epizootic and zoonotic risk (or a classic risk) to a pandemic threat (or a late modern risk). Vietnam’s response was part of its overall strategy to join the World Trade Organization and it was limited by Vietnam’s defence of its sovereignty. This strategy has been successful for Vietnam but has limited the possibility of cosmopolitan and democratic transformations. The case study highlights the constructed dimension of risks of late modernity and their possible instrumentalisation: it minimises the role of a community of fear relative to a community of trade.
Interword spacing effects on the acquisition of new vocabulary for readers of Chinese as a second language
Authors: Bai Xuejun , Liang Feifei , Blythe Hazel I. , Zang Chuanli , Yan Guoli , Liversedge Simon P.
Published: March 2013

We examined whether interword spacing would facilitate acquisition of new vocabulary for second language learners of Chinese. Participants' eye movements were measured as they read new vocabulary embedded in sentences during a learning session and a test session. In the learning session, participants read sentences in traditional unspaced format and half‐read sentences with interword spacing. In the test session, all participants read unspaced sentences. Participants in the spaced learning group read the target words more quickly than those in the unspaced learning group. This benefit was maintained at test, indicating that the manipulation enhanced learning of the novel words and was not a transient effect limited to occasions when interword spacing was present in the printed text. The insertion of interword spaces may allow readers to form a more fully specified representation of the novel word, or to strengthen connections between representations of the constituent characters and the multi‐character word.