bluuebunny/crossref_metadata_2025 huggingface dataset:
The Multifunctionality of Human Vγ9Vδ2 γδ T Cells: Clonal Plasticity or Distinct Subsets?
Authors: Kabelitz D. , He W.
Published: June 2012

The dominant subset of γδ T cells in human peripheral blood expresses Vγ9 paired with Vδ2 as variable TCR elements. Vγ9Vδ2 T cells recognize pyrophosphates derived from the microbial non‐mevalonate isoprenoid biosynthesis pathway at pico‐ to nanomolar concentrations. Structurally related pyrophosphates are generated in eukaryotic cells through the mevalonate pathway involved in protein prenylation and cholesterol synthesis. However, micromolar concentrations of endogenous pyrophosphates are required to be recognized by Vγ9Vδ2 T cells. Such concentrations are not produced by normal cells but can accumulate upon cellular stress and transformation. Therefore, many tumour cells are susceptible to γδ T cell–mediated lysis owing to the overproduction of endogenous pyrophosphates. This explains why Vγ9Vδ2 T cells contribute to both anti‐infective and anti‐tumour immunity. Ex vivo analysed Vγ9Vδ2 T cells can be subdivided on the basis of additional surface markers, including chemokine receptors and markers for naïve and memory T cells. At the functional level, Vγ9Vδ2 T cells produce a broad range of cytokines, display potent cytotoxic activity, regulate αβ T cell responses, and – quite surprisingly – can act as professional antigen‐presenting cells. Thus, an exceptional range of effector functions has been assigned to a population of T cells, which all recognize invariant exogenous or endogenous pyrophosphates that are not seen by any other immune cell. Here, we discuss whether this plethora of effector functions reflects the plasticity of individual Vγ9Vδ2 T cells or can be assigned to distinct subsets.
Targeted inactivation of transcription factors by overexpression of their truncated forms in plants
Authors: Seo Pil Joon , Hong Shin‐Young , Ryu Jae Yong , Jeong Eun‐Young , Kim Sang‐Gyu , Baldwin Ian T. , Park Chung‐Mo
Published: June 2012

Transcription factors are central constituents of gene regulatory networks that control diverse aspects of plant development and environmental adaptability. Therefore they have been explored for decades as primary targets for agricultural biotechnology. A gene of interest can readily be introduced into many crop plants, whereas targeted gene inactivation is practically difficult in many cases. Here, we developed an artificial small interfering peptide (a‐siPEP) approach, which is based on overexpression of specific protein domains, and evaluated its application for the targeted inactivation of transcription factors in the dicot model, Arabidopsis, and monocot model, Brachypodium. We designed potential a‐siPEPs of two representative MADS box transcription factors, SUPPRESSOR OF OVEREXPRESSOR OF CONSTANS 1 (SOC1) and AGAMOUS (AG), and a MYB transcription factor, LATE ELONGATED HYPOCOTYL (LHY). Transgenic plants overproducing the a‐siPEPs displayed phenotypes comparable to those of gene‐deficient mutants. The a‐siPEPs attenuate nuclear import and DNA‐binding of target transcription factors. Our data demonstrate that the a‐siPEP tool is an efficient genetic means of inactivating specific transcription factors in plants.
Jasmonic acid transient accumulation is needed for abscisic acid increase in citrus roots under drought stress conditions
Authors: de Ollas Carlos , Hernando Bárbara , Arbona Vicent , Gómez‐Cadenas Aurelio
Published: June 2012

Phytohormones are central players in sensing and signaling numerous environmental conditions like drought stress. In this work, an experimental system based on severe drought was established and hormone profiling together with gene expression of key enzymes involved in abscisic acid (ABA) and jasmonic acid (JA) biosynthesis was studied in roots of citrumelo CPB 4475 (a commercial citrus rootstock) plants. JA concentration transiently increased after a few hours of stress, returning to control levels 30 h after the onset of the condition. A more progressive ABA accumulation was observed, with the onset of this increase at the same time or right after the JA transient accumulation. Molecular data suggested that, at least, part of the hormonal regulation takes place at the biosynthetic level. These observations also pointed to a possible involvement of JA on ABA biosynthesis under stress. To test this hypothesis, JA and ABA biosynthesis were chemically inhibited and subsequently phenotypes rescued by the addition of exogenous hormones. Results showed that the early JA accumulation was necessary for the subsequent ABA increase in roots under stress whereas the opposite could not be stated. The model includes a burst of JA in roots of citrus under severe drought stress conditions that leads to a more progressive ABA accumulation that will induce later plant responses. The present work adds a new level of interaction between JA and ABA at the biosynthetic level that together with the previously described interaction between signal transduction cascades of the two hormones would allow plants to fine‐tune specific responses to different stimuli.
Interactive effects of UV radiation and water availability on seedlings of six woody Mediterranean species
Authors: Bernal Meritxell , Llorens Laura , Badosa Jordi , Verdaguer Dolors
Published: June 2012

To assess the effects of UV radiation and its interaction with water availability on Mediterranean plants, we performed an experiment with seedlings of six Mediterranean species (three mesophytes vs three xerophytes) grown in a glasshouse from May to October under three UV conditions (without UV, with UVA and with UVA+UVB) and two irrigation levels (watered to saturation and low watered). Morphological, physiological and biochemical measures were taken. Exposure to UVA+UVB increased the overall leaf mass per area (LMA) and the leaf carotenoids/chlorophyll a + b ratio of plants in relation to plants grown without UV or with UVA, respectively. In contrast, we did not find a general effect of UV on the leaf content of phenols or UVB‐absorbing compounds of the studied species. Regarding plant growth, UV inhibited the above‐ground biomass production of well‐watered plants of Pistacia lentiscus. Conversely, under low irrigation, UVA tended to abolish the reduction in growth experienced by P. lentiscus plants growing in a UV‐free environment, in accordance with UVA‐enhanced apparent electron transport rate (ETR) values under drought in this species. UVA also induced an overall increase in root biomass when plants of the studied species were grown under a low water supply. In conclusion, while plant exposition to UVA favored root growth under water shortage, UVB addition only gave rise to photoprotective responses, such as the increase in LMA or in the leaf carotenoids/chlorophyll a + b ratio of plants. Species‐specific responses to UV were not related with the xerophytic or mesophytic character of the studied species.
‘Myrosin cells’ are not a prerequisite for aphid feeding on oilseed rape (Brassica napus) but affect host plant preferences
Authors: Borgen B. H. , Ahuja I. , Thangstad O. P. , Honne B. I. , Rohloff J. , Rossiter J. T. , Bones A. M.
Published: June 2012

The enzyme myrosinase (EC 3.2.3.1.147) is present in specialised myrosin cells and forms part of the glucosinolate–myrosinase system, also known as ‘the mustard oil bomb’, which has an important role in the defence system of cruciferous plants against insect pests. Transgenic Brassica napus MINELESS have been produced by transgenic ablation of myrosin cells. This prompted us to investigate the importance of myrosin cells in plant–aphid interactions. In order to study this, we challenged transgenic MINELESS and wild‐type cultivar Westar seedlings with the aphids Brevicoryne brassicae (a specialist) and Myzus persicae (a generalist). Our study included aphid free‐choice and aphid fecundity experiments. Data from these experiments showed that B. brassicae prefers wild‐type seedlings and M. persicae prefers MINELESS. B. brassicae and M. persicae showed significant variation in establishment on plants regardless of whether they were wild type or MINELESS and also differed significantly in affecting plant parts. Myrosinase activity in MINELESS control seedlings was 83.6% lower than the wild‐type control seedlings. Infestation with either of the two aphid species induced myrosinase levels in both wild‐type and MINELESS seedlings. Infestation with M. persicae reduced the concentration of most glucosinolates while B. brassicae had the opposite effect. B. brassicae enhanced the formation of glucosinolate hydrolysis products both in wild‐type and MINELESS seedlings. However, M. persicae decreased All ITC but increased 3,4ETBut NIT in wild‐type seedlings. Taken together, the investigation shows that the presence of myrosin cells affects the preference of generalist and specialist aphid species for Brassica napus plants.
The periodic wetting of leaves enhances water relations and growth of the long‐lived conifer Araucaria angustifolia
Authors: Cassana F. F. , Dillenburg L. R.
Published: June 2012

The importance of foliar absorption of water and atmospheric solutes in conifers was recognised in the 1970s, and the importance of fog as a water source in forest environments has been recently demonstrated. Araucaria angustifolia (Araucariaceae) is an emergent tree species that grows in montane forests of southern Brazil, where rainfall and fog are frequent events, leading to frequent wetting of the leaves. Despite anatomical evidence in favour of leaf water absorption, there is no information on the existence and physiological significance of a such process. In this study, we test the hypothesis that the use of atmospheric water by leaves takes place and is physiologically relevant for the species, by comparing growth, water relations and nutritional status between plants grown under two conditions of soil water (well‐watered and water‐stressed plants) and three types of leaf spraying (none, water and nutrient solution spray). Leaf spraying had a greater effect in improving plant water relations when plants were under water stress. Plant growth was more responsive to water available to the leaves than to the roots, and was equally increased by both types of leaf spraying, with no interaction with soil water status. Spraying leaves with nutrient solution increased shoot ramification and raised the concentrations of N, P, K, Zn, Cu and Fe in the roots. Our results provide strong indications that water and nutrients are indeed absorbed by leaves of A. angustifolia, and that this process might be as important as water uptake by its roots.
Isolation and characterisation of an antifolate insensitive (afi1) mutant of Arabidopsis thaliana
Authors: Navarrete O. , Van Daele J. , Stove C. , Lambert W. , Storozhenko S. , Van Der Straeten D.
Published: June 2012

Antifolates can impair the synthesis and/or function of folates in living organisms. Mechanisms of resistance or tolerance to antifolates have been mainly described in plants using the drug methotrexate. In this work, the antifolate trimethoprim (TMP) was used with the aim of revealing a novel mechanism of resistance. EMS mutagenised seeds from Arabidopsis were screened to isolate individuals insensitive to TMP. Genetic analysis revealed a homozygous recessive mutation that segregates with the phenotype of tolerance to 50 μm TMP. Mapping analysis localised the mutation at the end of the short arm of chromosome 3. Preliminary characterisation demonstrated up‐regulation of several genes from the folate biosynthetic pathway in the TMP insensitive mutant, and a slight increase in total folate content in the mutant as compared with the Col‐0 control. Moreover, sequence analysis of the DHFR (dihydrofolate reductase) genes, which encode a known target for resistance to antifolates, did not reveal any changes. This study is the first report of a stable mutant insensitive (afi1) to the antifolate trimethoprim in plants, and suggests the existence of a novel mechanism of resistance to antifolates.
The GCN2 homologue in Arabidopsis thaliana interacts with uncharged tRNA and uses Arabidopsis eIF2α molecules as direct substrates
Authors: Li M.‐W. , AuYeung W.‐K. , Lam H.‐M.
Published: June 2012

Phosphorylation of eIF2α is an important strategy for living organisms to adapt to metabolic and physiological changes that are often associated with external stimuli. GCN2 is one of the well‐studied eIF2α kinases in yeast and mammals, which is responsible for the survival of the organism under amino acid starvation. Despite the downstream reactions being quite divergent, AtGCN2 exhibits a high primary sequence similarity to its yeast and animal counterparts. In this study, we provide experimental evidence to show that AtGCN2 shares similar biochemical properties to the yeast and animal homologues. Our in vitro assays demonstrate the binding of the C‐terminus of AtGCN2 to uncharged tRNA molecules and the enzymatic activities of AtGCN2 on both eIF2α homologues in A. thaliana, thus providing essential information for further understanding the functions of plant general control non‐repressible (GCN) homologues.
The partitioning of water uptake between growth forms in a Neotropical savanna: do herbs exploit a third water source niche?
Authors: Rossatto D. R. , da Silveira Lobo Sternberg L. , Franco A. C.
Published: June 2012

In addition to trees and grasses, the savannas of central Brazil are characterised by a diverse herbaceous dicot flora. Here we tested whether the coexistence of a highly diversified assemblage of species resulted in stratification or strong overlap in the use of soil water resources. We measured oxygen and hydrogen isotope ratios of stem water from herbs, grasses and trees growing side by side, as well as the isotopic composition of water in soil profile, groundwater and rainfall, and predawn (Ψpd) and midday (Ψmd) leaf water potentials. We used a stable isotope mixing model to estimate vertical partitioning of soil water by the three growth forms. Grasses relied on shallow soil water (5–50 cm) and were strongly anisohydric. Ψpd and Ψmd decreased significantly from the wet to the dry season. Trees extracted water from deeper regions of the soil profile (60–120 cm) and were isohydric. Ψpd and Ψmd did not change from the wet to the dry season. Herbs overlapped with grasses in patterns of water extraction in the dry season (between 10 and 40 cm), but they took up water at soil depths intermediate (70–100 cm) to those of trees and grasses during the wet season. They showed seasonal changes in Ψpd but not in Ψmd. We conclude that vertical partitioning of soil water may have contributed to coexistence of these three growth forms and resulted in a more complex pattern of soil water extraction than the two‐compartment model of soil water uptake currently used to explain the structure and function of tropical savanna ecosystems.
Melanin‐Based Coloration in Juvenile Kestrels (Falco tinnunculus) Covaries with Anti‐Predatory Personality Traits
Authors: van den Brink Valentijn , Henry Isabelle , Wakamatsu Kazumasa , Roulin Alexandre
Published: June 2012

Recent studies have shown that melanin‐based coloration is associated with the ability to cope with stressful environments, potentially explaining why coloration covaries with anti‐predator behaviours, boldness and docility. To investigate whether these relationships are consistent across species, we performed a study in the European kestrel (
Falco tinnunculus). Similar to our results found previously in the barn owl (
Tyto alba), nestling kestrels displaying a larger sub‐terminal black tail band stayed on their back longer (tonic immobility test) and breathed at a lower rate than individuals with a smaller black band when handled. However, in contrast to barn owls, nestling kestrels with a larger black tail band were more aggressive and more agitated. Our results strengthen the hypothesis that melanin coloration is related to stress response and in turn to the reaction to predators, a very important personality trait (i.e. boldness).
Heightened cough response to bronchoconstriction in cough variant asthma
Authors: OHKURA NORIYUKI , FUJIMURA MASAKI , NAKADE YUSUKE , OKAZAKI AKIHITO , KATAYAMA NOBUYUKI
Published: June 2012

Background and objective:  The pathophysiology of cough variant asthma (CVA) is poorly understood. We compared bronchoconstriction‐triggered cough between CVA patients and normal control (NC) subjects.

Methods:  There were two protocols in the study. We measured bronchial responsiveness to methacholine (MCh) and counted the number of coughs in nine CVA patients and seven NC subjects (Study A). Using partial and full flow–volume curves, expiratory flow of the partial flow–volume curve at 40% above residual volume level (PEF40) and FEV1 were used to measure bronchoconstriction. Mild bronchoconstriction was defined as a 35% fall in PEF40 (PC35‐PEF40), and more severe bronchoconstriction as a 20% fall in FEV1 (PC20‐FEV1). In study B, the same measurements were obtained in six CVA patients before and after therapy.

Results:  In study A, more coughs were provoked at PC35‐PEF40 in CVA patients (median, 60 coughs/32 min post challenge; range, 12–135) than in NC subjects (median, 0/32 min; range, 0–13; P < 0.05). At PC20‐FEV1, more coughs were provoked in CVA patients (median, 60/32 min; range, 12–150) than in NC subjects (median, 20/32 min; range, 0–54; P < 0.05). In study B, the six CVA patients who underwent re‐examination after treatment had less coughs at PC35‐PEF40 (median, 3/32 min; range, 0–14) and PC20‐FEV1 (median, 13/32 min; range, 3–26) after therapy than before therapy (median, 54/32 min; range, 33–125 and 52/32 min, 45–96, respectively; P < 0.05).

Conclusions:  We identified heightened cough response to bronchoconstriction as a feature of CVA.
Differential involvement of the basolateral amygdala and orbitofrontal cortex in the formation of sensory‐specific associations in conditioned flavor preference and magazine approach paradigms
Authors: Scarlet Janina , Delamater Andrew R. , Campese Vincent , Fein Matthew , Wheeler Daniel S.
Published: June 2012

Four experiments examined the roles of the basolateral amygdala and orbitofrontal cortex in the formation of sensory‐specific associations in conditioned flavor preference and conditioned magazine approach paradigms using unconditioned stimulus (US) devaluation and selective Pavlovian‐instrumental transfer procedures in Long Evans rats. Experiment 1 found that pre‐training amygdala and orbitofrontal cortex lesions had no detectable effect on the formation or flexible use of sensory‐specific flavor–nutrient associations in a US devaluation task, where flavor cues were paired either simultaneously or sequentially with nutrient rewards in water‐deprived subjects. In Experiment 2, pre‐training amygdala and orbitofrontal cortex lesions both attenuated outcome‐specific Pavlovian‐instrumental transfer. Experiment 3 indicated that amygdala lesions have no effect on the formation of sensory‐specific flavor–nutrient associations in a US devaluation task in food‐deprived subjects. Finally, Experiment 4 demonstrated that the outcomes used in Experiment 3 were sufficiently motivationally significant to support conditioned flavor preference. These findings suggest that, although both orbitofrontal cortex and amygdala lesions attenuate the acquisition of sensory‐specific associations in magazine approach conditioning, neither lesion reduces the ability to appropriately respond to a flavor cue that was paired with a devalued outcome.
Protoanemonin: a natural quorum sensing inhibitor that selectively activates iron starvation response
Authors: Bobadilla Fazzini Roberto A. , Skindersoe Mette E. , Bielecki Piotr , Puchałka Jacek , Givskov Michael , Martins dos Santos Vitor A. P.
Published: June 2012

Many Gram‐negative bacteria employ cell‐to‐cell communication mediated by N‐acyl homoserine lactones (quorum sensing) to control expression of a wide range of genes including, but not limited to, genes encoding virulence factors. Outside the laboratory, the bacteria live in complex communities where signals may be perceived across species. We here present a newly found natural quorum sensing inhibitor, produced by the pseudomonads Pseudomonas sp. B13 and Pseudomonas reinekei MT1 as a blind end in the biodegradation of organochloride xenobiotics, which inhibits quorum sensing in P. aeruginosa in naturally occurring concentrations. This catabolite, 4‐methylenebut‐2‐en‐4‐olide, also known as protoanemonin, has been reported to possess antibacterial properties, but seems to have dual functions. Using transcriptomics and proteomics, we found that protoanemonin significantly reduced expression of genes and secretion of proteins known to be under control of quorum sensing in P. aeruginosa. Moreover, we found activation of genes and gene products involved in iron starvation response. It is thus likely that inhibition of quorum sensing, as the production of antibiotics, is a phenomenon found in complex bacterial communities.
In vivo imaging reveals novel aspects of retinal disease progression in Rs1h−/Y mice but no therapeutic effect of carbonic anhydrase inhibition
Authors: Zhour Ahmad , Bolz Sylvia , Grimm Christian , Willmann Gabriel , Schatz Andreas , Weber Bernhard H. F. , Zrenner Eberhart , Fischer M. Dominik
Published: June 2012

Purpose  X‐linked juvenile retinoschisis (XLRS) is the most common juvenile maculopathy in men and is caused by mutations in the gene encoding retinoschisin (RS1). Evidence in the literature on the therapeutic effect of carboanhydrase inhibitors (CAIs) to treat schisis formation in the retina has remained equivocal. Here, we evaluate the effect of the CAI dorzolamide on the structural and functional disease progression in the mouse model for XLRS (Rs1h−/y).

Methods  Rs1h

−/y
mice were treated unilaterally with dorzolamide eye drops (Trusopt® 20 mg/mL) every 12 h for 2 weeks starting on postnatal day 14 (n = 27). Changes of retinal structure were monitored by confocal scanning laser ophthalmoscopy and spectral domain optical coherence tomography 12 h, 14 days, 4 weeks, 2 months, and 6 months after completion of the treatment.

Results  Schisis formation (peak at 3 months) preceded photoreceptor degeneration and hyper‐fluorescence (peak at 7 months). Structural pathology was most severe in the superior hemi‐retina with previously unreported hyper‐fluorescent lesions. Quantitative analysis showed no significant differences regarding the inner or outer retinal thickness of the treated vs. untreated eyes 12 h after the completion of treatment (IRT12 h = −1.29 ± 1.89 μm; ORT12 h = 0.61 ± 2.08 μm; mean ± 95%CI) or at any later time point.

Conclusion  Time line analysis after short‐term treatment with CAI failed to show short‐, intermediate‐, or long‐term evidence of structural improvement in Rs1h−/y mice. Schisis formation in the inner retina peaked at the age of 3 months and was followed by photoreceptor degeneration predominantly in the superior hemi‐retina. Previously unreported hyper‐fluorescent lesions co‐register with structural retinal pathologies.
Drivers for change in the management of prostate cancer – Guidelines and new treatment techniques
Authors: Wolff J.M. , Mason M.
Published: June 2012

Clinical practice guidelines and new treatment techniques are of particular importance for the effective management of prostate cancer. In Europe, the European Association of Urology guidelines offer a regularly updated evidence‐based source of recommendations for the optimal treatment of prostate cancer. This review examines recent changes to guidelines highlighting developments in diagnosis, hormonal therapy in advanced and metastatic disease, bone protection, the definition of new terminology such as castrate‐resistant prostate cancer, treatment of relapse after hormonal therapy, and cytotoxic therapy for castrate‐resistant prostate cancer. The review also examines new surgical and radiotherapeutic developments in prostate cancer. This includes minimally invasive techniques such as robot‐assisted radical prostatectomy, which is becoming the surgical gold standard for clinically localized disease in many countries. Other promising techniques reviewed include cryosurgical ablation of the prostate, laser‐induced interstitial thermotherapy, vascular‐targeted photodynamic therapy, and high‐intensity focused ultrasound; with the exception of cryotherapy, these approaches are not currently recommended for routine clinical use. Finally, we will review the evidence supporting intensity modulated radiotherapy, an optimized high‐precision form of three‐dimensional conformal radiotherapy which aims to allow homogeneously increased radiation doses, without increased toxicity to healthy at‐risk organs. Novel techniques such as proton beam or carbon ion radiotherapy, which may offer improved and more localized dose distribution with reduced damage to normal tissue, are also examined.
Coeliac disease in Type 1 diabetes from 1990 to 2009: higher incidence in young children after longer diabetes duration
Authors: Pham‐Short A. , Donaghue K. C. , Ambler G. , Chan A. K. , Craig M. E.
Published: June 2012

Diabet. Med. 29, e286‐e289 (2012)

Aims  To determine the incidence of coeliac disease in young people with Type 1 diabetes and to examine the effect of age at diabetes onset and disease duration.

Methods  This was a clinic‐based observational cohort study of 4379 people aged ≤ 18 years (49% male) between 1990 and 2009 from Sydney, Australia. Screening for coeliac disease was performed at diagnosis and 1–2 yearly using anti‐endomysial and/or anti‐tissue transglutaminase immunoglobulin A (IgA) antibodies. Coeliac disease was diagnosed by small bowel biopsy based on Marsh score ≥ III.

Results  Coeliac disease was confirmed by biopsy in 185; of these, 61 (33%) were endomysial or tissue transglutaminase IgA antibody‐positive at diabetes diagnosis. Mean age at diabetes onset was 6.6 ± 4.0 vs. 8.4 ± 4.1 years in those without coeliac disease (P < 0.001). Mean incidence was 7.7 per 1000 person years (95% CI 6.6–8.9) over 20 years. Incidence was higher in children aged < 5 years at diabetes diagnosis (10.4 per 1000 person years) vs. ≥ 5 years (6.4 per 1000), incidence rate ratio 1.6 (95% CI 1.2–2.2, P = 0.002). Coeliac disease was diagnosed after 2, 5 and 10 years of diabetes in 45, 78 and 94% of cases, respectively. Median time to coeliac disease diagnosis was longer in children aged < 5 years at diabetes onset (3.3 years) compared with older children (0.7 years, P < 0.001).

Conclusions  Coeliac disease is common in young people with Type 1 diabetes; the risk is greatest with diabetes onset < 5 years, but after longer diabetes duration. Screening for coeliac disease should be performed at diabetes diagnosis and for at least 10 years in young children.
Dorothy Hodgkin Lecture 2012* Non‐alcoholic fatty liver disease, insulin resistance and ectopic fat: a new problem in diabetes management
Authors: Byrne C. D.
Published: June 2012

Diabet. Med. 29, 1098–1107 (2012)

Non‐alcoholic fatty liver disease is now recognized as the hepatic component of the metabolic syndrome. Non‐alcoholic fatty liver disease is a spectrum of fat‐associated liver conditions that can result in end‐stage liver disease and the need for liver transplantation. Simple steatosis, or fatty liver, occurs early in non‐alcoholic fatty liver disease and may progress to non‐alcoholic steatohepatitis, fibrosis and cirrhosis with increased risk of hepatocellular carcinoma. Prevalence estimates for non‐alcoholic fatty liver disease range from 17 to 33% in the general populations and it has been estimated that non‐alcoholic fatty liver disease exists in up to 70% of people with Type 2 diabetes. Non‐alcoholic fatty liver disease increases risk of Type 2 diabetes and cardiovascular disease. In people with Type 2 diabetes, non‐alcoholic fatty liver disease is the most frequent cause (∼80%) of fatty liver diagnosed by ultrasound. As non‐alcoholic fatty liver disease is strongly associated with insulin resistance, the presence of non‐alcoholic fatty liver disease with diabetes often contributes to poor glycaemic control. Consequently, strategies that decrease liver fat and improve whole‐body insulin sensitivity may both contribute to prevention of Type 2 diabetes and to better glycaemic control in people who already have developed diabetes. This review summarizes the Dorothy Hodgkin lecture given by the author at the 2012 Diabetes UK annual scientific conference, proposing that fatty acid fluxes through the liver are crucial for the pathogenesis of non‐alcoholic fatty liver disease and for increasing insulin resistance.
Harnessing Innovation for Change: Sustainability and Poverty in Developing Countries
Authors: Khavul Susanna , Bruton Garry D.
Published: June 2012

abstract

To date, a well‐developed business perspective on how to promote sustainability for those in poverty is sorely lacking. For sustainability enhancing innovations in developing countries, poverty presents unique challenges. In this paper, we argue that if sustainability enhancing innovations introduced in developing countries are to stick, they need to be designed with local customers, networks, and business ecosystems in mind. We illustrate this view using case examples from mobile telephony, fuel efficient stoves, clean drinking water, and household electrification. Our paper underscores the need for today's managers to understand poverty as an integral part of the sustainability nexus and the new international business equation.
For Rigour in Organizational Management Theory Research
Authors: Donaldson Lex , Qiu Jane , Luo Ben Nanfeng
Published: June 2012

abstract

Rigour is required in examining the empirical validity of theories in organizational management, and is often considered to be the opposite of creativity in the development of knowledge about managing organizations. In this article, we argue that rigour is necessary in the enterprise of organizational management research. Moreover, it can actually be a contributor to creativity. The issue is not rigour versus creativity, but rather how rigour can foster creativity. We show that rigour in both theory and methodology can foster creativity. Rigour in theory provides the logical thinking that is the foundation that allows the development of sound theory. This can be achieved in various ways, including theory building, mathematical modelling, causal modelling, and theory analysis. Rigour in methodology can assist creativity in quantitative integration. The contribution of rigour to creativity is evidenced by the recently created statistico‐organizational theory and other new advancements in the field of structural contingency research.
A systematic review of the impact of weight loss on cancer incidence and mortality
Authors: Birks S. , Peeters A. , Backholer K. , O'Brien P. , Brown W.
Published: June 2012

Obesity is well recognized as a significant risk factor for certain cancers; however, a corresponding risk reduction with weight loss is not yet clearly defined. This review aims to examine the literature investigating the effect of all types of weight loss on cancer incidence and mortality, and to more clearly describe the relationship between these two factors. A literature search identified 34 publications reporting weight loss data in relation to cancer incidence or mortality. All except one were observational studies and the majority used self‐reported weights and did not define intentionality of weight loss. 16/34 studies found a significant inverse association between weight loss and cancer incidence or mortality. The remainder returned null findings. The observed association was more consistently seen in studies that investigated the effect of intentional weight loss (5/6 studies) and the risk reduction was greatest for obesity‐related cancers and in women. In conclusion, intentional weight loss does result in a decreased incidence of cancer, particularly female obesity‐related cancers. However, there is a need for further evaluation of sustained intentional weight loss in the obese with less reliance on self‐reported weight data and more focus on male populations.
A Generalized Framework for Parallelizing Traffic Sign Inventory of Video Log Images Using Multicore Processors
Authors: Tsai Yichang , Huang Yuchun
Published: June 2012

Abstract:  Video log images could potentially be used for state transportation agencies to automatically inventory traffic sign assets. However, processing millions of video log images is prohibitively time‐consuming. Taking advantage of the emerging chip multicore processor (CMP) technology, this article proposes a generalized framework for parallelizing traffic sign detection in a large number of high‐resolution video log images. Based on an improved contour finding and workload identification strategy, task and data parallelism in traffic sign detection are fully developed at multiple levels. A generalized parallelization framework for dynamic workload scheduling using adaptive work‐stealing of thread pool and dynamic circular lock‐free double‐ended queue is then proposed. Experimental results on 14,514 images provided by the Louisiana Department of Transportation show that the parallelized traffic sign detection algorithm has great potential to improve computation time with a parallel speedup of up to 18 times on multilevel parallel configurations and different CMP platforms while keeping the same accuracy as the serial version.
Transaction Cost Economics and Open Innovation: Implications for Theory and Practice
Authors: Remneland‐Wikhamn Björn , Knights David
Published: June 2012

Transaction cost economics (TCE) has had a strong impact on theories of economic exchange but also on open innovation, even though the relationship is often implicit rather than explicit. In this paper, we highlight what we consider to be the problematic use of TCE in the context of open innovation, suggesting that it has a limited descriptive power and potentially does normative damage to open innovation practice. A case study of the Volvo Group will be drawn upon to illustrate these claims. The case questions the belief that hierarchical control eliminates transaction costs. Also, it suggests that an overemphasis on calculative reduction of transaction costs together with a focus on governance and rationality leave little space for an innovative climate, thus diverting attention away from the creative potential of transactions. Indeed the self‐fulfilling prophecy character of subscribing to the assumptions of TCE may not merely limit but actually undermine innovation.
Multiple minimally invasive Erbium: Yttrium Aluminum Garnet laser mini‐peels for skin rejuvenation: an objective assessment
Authors: El‐Domyati Moetaz , El‐Ammawi Tarek S. , Medhat Walid , Moawad Osama , Mahoney Mỹ G. , Uitto Jouni
Published: June 2012

Background  As the demand for minimally invasive rejuvenation is increasing, micropeel resurfacing using Erbium:Yttrium Aluminum Garnet (Er:YAG) laser 2940 nm has been reported for the treatment of photoaged skin without ablation of the epidermis. However, little is known about the efficacy and underlying histologic changes associated with this type of treatment.

Aims  The aims of this study are to evaluate the clinical effect and objectively quantify the histological changes in response to multiple sessions of Er:YAG laser 2940 nm mini‐peels.

Patients and methods  Six female volunteers of Fitzpatrick skin type III–IV and Glogau’s class I–III wrinkles were subjected to six microresurfacing peels at 2‐week intervals using Er:YAG 2940 nm laser at subablative fluences of 2–3 J/cm2 to treat periorbital rhytides. Quantitative evaluation of collagen types I, III, and VII, newly synthesized collagen, total elastin, and tropoelastin was performed by histochemistry and immunohistochemistry coupled with computerized morphometric analysis at base line, end of treatment, and 3 months post‐treatment.

Results  Compared to the base line, evaluation of volunteers revealed obvious clinical improvement in response to Er:YAG mini‐peels. Collagen types I, III, and VII, as well as newly synthesized collagen, together with tropoelastin showed a statistically significant increase in response to treatment, while the mean level of total elastin was significantly decreased in response to treatment. However, this was followed by regression of improvement at 3 months post‐treatment but was still better than baseline.

Conclusions  This study revealed that multiple Er:YAG mini‐peels is a promising treatment option for photoaging as it reverses the signs of photoaged skin with little downtime and side effects. However, to maintain the short‐term improvement achieved after treatment, continued Er:YAG 2940 nm laser mini‐peels is required.
Long‐term aesthetic outcomes with injectable poly‐l‐lactic acid: observations and practical recommendations based on clinical experience over 5 years
Authors: Rendon Marta I
Published: June 2012

Background  Facial rejuvenation techniques have evolved in recent decades driven by a paradigm shift to restoration of lost volume, and an increase in the number of available products. As clinical experience has increased, practitioners have further refined the use of these products.

Objectives  To share observations and practical recommendations based on clinical experience with the aesthetic use of injectable poly‐l‐lactic acid (PLLA) in patients followed for up to 5 years.

Methods  Literature review and retrospective case history review of the first 100 patients treated with injectable PLLA, many of whom have been followed for over 5 years.

Results  Use of injectable PLLA, alone or in combination with other products, has provided excellent and long‐lasting (up to 5 years) aesthetic results for most of the reviewed patients. Typically, patients have received one or two touch‐up sessions between years 2 and 4 after initial full correction. There were minimal adverse events of papule formation; these eventually resolved.

Conclusions  Injectable PLLA is a safe and effective option for achieving long‐term patient satisfaction with soft‐tissue augmentation.
Effects of Solar Radiation on the Skin
Authors: Polefka Thomas G , Meyer Thomas A , Agin Patricia P , Bianchini Robert J
Published: June 2012

No one would underestimate the importance of sunlight to the evolution of life on the earth and its role in human development. However, all humans – especially individuals who are lightly pigmented or whose occupation or lifestyle exposes them to excessive amounts of sunlight – are potentially susceptible to its deleterious effects. These effects can range from acute biological responses, such as sunburn and skin tanning, to conditions resulting from chronic exposure such as photoaged skin and potentially life‐threatening conditions such as skin cancer. The objective of this review is to present a concise and up‐to‐date perspective on the effects of UVB, UVA, visible, and infrared radiation on cutaneous biochemistry and physiology.
Hair transplant for acne scars: an innovative approach
Authors: Sarangal Rishu , Yadav Savita , Dogra Sunil
Published: June 2012

Postacne scarring is a common entity that affects patients both physically and psychologically. Treatment of facial scarring is rarely a mono‐dimensional process. Various modalities of treatments from cheaper subcision, punch techniques and excision to expensive laser resurfacing techniques are available. Treatment of postacne scars in a particular case has to be individualized, taking into consideration many factors like age, gender, types of scarring, Fitzpatrick skin type, and socioeconomic status of the patient. In this article, we describe an innovative method of simply doing hair transplantation in acne scars and hence making them less visible and cosmetically well acceptable to the patient.
Role of Adrenal Glucocorticoid Signaling in Prefrontal Cortex Gene Expression and Acute Behavioral Responses to Ethanol
Authors: Costin Blair N. , Wolen Aaron R. , Fitting Sylvia , Shelton Keith L. , Miles Michael F.
Published: June 2012

Background

Glucocorticoid hormones modulate acute and chronic behavioral and molecular responses to drugs of abuse including psychostimulants and opioids. There is growing evidence that glucocorticoids might also modulate behavioral responses to ethanol (
EtOH
). Acute
EtOH
activates the hypothalamic–pituitary–adrenal axis, causing the release of adrenal glucocorticoid hormones. Our prior genomic studies suggest that glucocorticoids play a role in regulating gene expression in the prefrontal cortex (PFC) of DBA2/J (D2) mice following acute
EtOH
administration. However, few studies have analyzed the role of glucocorticoid signaling in behavioral responses to acute
EtOH
. Such work could be significant, given the predictive value for the level of response to acute
EtOH
in the risk for alcoholism.

Methods

We studied whether the glucocorticoid receptor (GR) antagonist, RU‐486, or adrenalectomy (ADX) altered male D2 mouse behavioral responses to acute (locomotor activation, anxiolysis, or loss‐of‐righting reflex [LORR]) or repeated (sensitization)
EtOH
treatment. Whole‐genome microarray analysis and bioinformatics approaches were used to identify PFC candidate genes possibly responsible for altered behavioral responses to
EtOH
following ADX.

Results

ADX and RU‐486 both impaired acute
EtOH
(2 g/kg)‐induced locomotor activation in D2 mice without affecting basal locomotor activity. However, neither ADX nor RU‐486 altered the initiation of
EtOH
sensitization (locomotor activation or jump counts),
EtOH
‐induced anxiolysis, or LORR. ADX mice showed microarray gene expression changes in PFC that significantly overlapped with acute
EtOH
‐responsive gene sets derived by our prior microarray studies. Q‐rtPCR analysis verified that ADX decreased PFC expression of
Fkbp5 while significantly increasing
Gpr6 expression. In addition, high‐dose RU‐486 pretreatment blunted
EtOH
‐induced
Fkbp5 expression.

Conclusions

Our studies suggest that
EtOH
's activation of adrenal glucocorticoid release and subsequent GR activation may partially modulate
EtOH
's acute locomotor activation in male D2 mice. Furthermore, because adrenal glucocorticoid basal tone regulated PFC gene expression, including a significant set of acute
EtOH
‐responsive genes, this suggests that glucocorticoid‐regulated PFC gene expression may be an important factor modulating acute behavioral responses to
EtOH
.
The Phosphodiesterase‐4 (PDE4) Inhibitor Rolipram Decreases Ethanol Seeking and Consumption in Alcohol‐Preferring Fawn‐Hooded Rats
Authors: Wen Rui‐Ting , Zhang Min , Qin Wang‐Jun , Liu Qing , Wang Wei‐Ping , Lawrence Andrew J. , Zhang Han‐Ting , Liang Jian‐Hui
Published: June 2012

Background

Alcohol dependence is a complex psychiatric disorder demanding development of novel pharmacotherapies. Because the cyclic adenosine monophosphate (cAMP) signaling cascade has been implicated in mediating behavioral responses to alcohol, key components in this cascade may serve as potential treatment targets. Phosphodiesterase‐4 (PDE4), an enzyme that specifically catalyzes the hydrolysis of cAMP, represents a key point in regulating intracellular cAMP levels. Thus, it was of interest to determine whether PDE4 was involved in the regulation of alcohol use and abuse.

Methods

Male Fawn‐Hooded (FH/Wjd) rats were tested for 5% (v/v) ethanol (EtOH) and 10% (w/v) sucrose operant oral self‐administration following treatment with the selective PDE4 inhibitor rolipram (0.0125, 0.025, or 0.05 mg/kg, subcutaneous [s.c.]); rolipram at higher doses (0.05, 0.1, and 0.2 mg/kg, s.c.) was tested to determine its impact on the intake of EtOH, sucrose, or water using the 2‐bottle choice drinking paradigm. Subsequent open‐field testing was performed to evaluate the influence of higher doses of rolipram on locomotor activity.

Results

Acute administration of rolipram dose‐dependently reduced operant self‐administration of 5% EtOH, but had no effect on 10% sucrose responding. Time‐course assessment revealed significant decreases in EtOH consumption after rolipram (0.1, 0.2 mg/kg) treatment in continuous‐ and intermittent access to EtOH at 5% or 10%, respectively. Moreover, chronic rolipram treatment time‐dependently decreased 5% EtOH consumption and preference during treatment days and after the termination of rolipram administration. Rolipram at the highest doses (0.1 and 0.2 mg/kg) did decrease locomotor activity, but the effect lasted only 10 and 20 minutes, respectively, which did not likely alter long‐term EtOH drinking.

Conclusions

These results suggest that PDE4 plays a role in alcohol seeking and consumption behavior. Drugs interfering with PDE4 may be a potential pharmacotherapy for alcohol dependence.
Dominant Language Transfer in Spanish Heritage Speakers and Second Language Learners in the Interpretation of Definite Articles
Authors: MONTRUL SILVINA , IONIN TANIA
Published: June 2012

This study investigates dominant language transfer (from English) in adult Spanish second language (L2) learners and Spanish heritage speakers. We focus on contrasting properties of English and Spanish definite articles with respect to generic reference (‘Elephants have ivory tusks’ vs.Loselefantes tienen colmillos de marfil) and inalienable possession (‘Peter raised his hand’ vs.Pedro levantólamano). Thirty adult Spanish heritage speakers and 30 L2 learners of Spanish completed four written tasks (acceptability judgment, truth‐value judgment, picture‐sentence matching, and sentence‐picture acceptability judgment). The results show that the heritage speakers and the L2 learners exhibited dominant language transfer from English with the interpretation of definite articles in generic contexts; transfer effects were not as pronounced in the inalienable possession construction. We discuss the implications of these findings for heritage language research and teaching.
Lexicalized Aspectual Usage in Oral Proficiency Interviews
Authors: ROBIN RICHARD M.
Published: June 2012

This study suggests that Intermediate High and Advanced speakers produce aspectually valid constructions in Oral Proficiency Interviews (OPIs) in large part because they are doing more than assigning aspect to lexical categories (Lexical aspect hypothesis), but because they are assigning lexicalized meaning to discrete verbs, for example govorit’ (imperfective)—‘to talk,’ but skazat’ (perfective)—‘to say.’ Analysis of the data from 55 OPIs conducted with second language (L2) Russian speakers ranging from Intermediate High to Superior confirms three hypotheses: (a) the proportion of aspectual utterances that owe their correctness to lexicalization decreases as proficiency increases; (b) aspectual competence as demonstrated by the greater number of aspectually non‐lexicalized verbs in the speech of L2 Russian speakers rises with proficiency level; (c) a decrease in the proportion of lexicalized verbs in an examinee's speech correlates positively with an increase in the variety of verbs used. Other findings include a relative paucity of unprefixed verbs of motion in the corpus and a high ratio of lexicalized forms of skazat’‘to say,’ and their distribution did not correlate with proficiency levels in either direction. The high ratio of aspectually lexicalized items in the corpus and the aspectual inaccuracies to which they lead have implications for teaching students who are approaching Intermediate High and Advanced levels of proficiency.
Entrepreneurship in Innovation Ecosystems: Entrepreneurs’ Self–Regulatory Processes and Their Implications for New Venture Success
Authors: Nambisan Satish , Baron Robert A.
Published: June 2012

Innovation ecosystems have emerged as an important context for entrepreneurship. Ecosystem entrepreneurs, however, face a unique set of challenges associated with the need to balance the goals and priorities set by the ecosystem leader with the goals and priorities of the new venture. We focus on ecosystem entrepreneurs’ self–regulatory processes and the potential role of these processes in entrepreneurs’ efforts to successfully balance requirements set by the ecosystem leader with the goals of their own ventures.