The role of AIP and CDKN1B/p27Kip1 in endocrine neoplasia

Identification of genes predisposing to tumor syndromes has raised general awareness of tumorigenesis. Genetic testing of tumor susceptibility genes aids the recognition of individuals at increased risk of tumors. Identification of novel predisposing genes enables further studies concerning the classification of potential associated tumors and the definition of target patient group. Pituitary adenomas are common, benign neoplasms accounting for approximately 15% of all intracranial tumors. Accurate incidence estimation is challenging since a great portion of these adenomas are small and asymptomatic. Clinically relevant adenomas, that cause symptoms due to the expansion of the cell mass or the over-secretion of normally produced hormones, occur in approximately one of 1 000 individuals. Although the majority of pituitary adenomas are sporadic, a minority occur as components of familial syndromes, such as Multiple Endocrine Neoplasia type 1 (MEN1) and Carney complex (CNC). MEN1 syndrome is caused by germ-line mutations in the MEN1 gene, whereas most of the CNC patients carry the mutated protein kinase A (PKA) regulatory subunit-1-α (PRKAR1A) gene. Recently, other conditions predisposing to endocrine tumors have been identified: Pituitary Adenoma Predisposition (PAP) and MEN type 4 (MEN4). PAP was originally identified in a genetically homogeneous Finnish population. In a population based cohort from Northern Finland, aryl hydrocarbon receptor-interacting protein (AIP) gene mutations were found in 16% of all patients diagnosed with growth hormone (GH) producing pituitary adenoma, and in 40% of the subset of patients who were diagnosed under the age of 35 years. Since AIP mutations were originally described in a defined, homogeneous population from Northern Finland, it was relevant to study whether mutations also occur in more heterogeneous populations. In patient cohorts with different ethnic origins and variable clinical phenotypes, germ-line AIP mutations were detectable at low frequencies (range 0.8-7.4%). AIP mutation-positive patients were often diagnosed with a GH-producing adenoma at a young age, and usually had no family history of endocrine tumors. The low frequency of AIP mutations in randomly selected patients, and the lack of any family history of pituitary adenomas create a challenge for the identification of PAP patients. Our preliminary study suggests that AIP immunohistochemistry may serve as a pre-screening tool to distinguish between the AIP mutation-negative and the mutation-positive tumors. Tumors of various endocrine glands are components of MEN1 and CNC syndromes. Somatic MEN1 and PRKAR1A mutations in sporadic pituitary adenomas are rare, but occur in some of the other tumors related to these syndromes. The role of AIP mutations in endocrine neoplasia was studied and our results indicated that somatic AIP mutations are rare or non-existent in sporadic tumors of endocrine glands (0 of 111). Furthermore, germ-line AIP mutations in prolactin producing adenomas (2 of 9) confirmed the role of this pituitary tumor type in the PAP phenotype. Thyroid disorders are common in the general population, and the majority of them are sporadic. Interestingly, it has been suggested that thyroid disorders might be more common in PAP families. For this reason we studied germ-line AIP mutations in 93 index cases from familial non-medullary thyroid cancer (NMTC) families. The underlying gene or genes for familial NMTC have not been identified yet. None of the patients had any potentially pathogenic AIP mutation. This suggests that AIP is unlikely to play a role in familial NMTCs. A novel multiple endocrine syndrome was originally described in rats with phenotypic features of human MEN type 1 and 2. Germ-line mutations of cyclin-dependent kinase inhibitor 1B (CDKN1B also known as p27Kip1) gene were reported later in these rats and a germ-line mutation was also identified in one human family with MEN1-like phenotype (later named MEN4). To confirm the importance of this gene’s mutations in humans, we performed a mutation screening in MEN-like patients and in patients with pituitary adenoma. Our results indicate that CDKN1B/p27Kip1 mutations appear in a small portion of MEN1-like patients (one of 36), and that such mutations are rare or non-existent in both familial (0 of 19) and sporadic pituitary adenoma patients (0 of 50). In conclusion, this work strengthens the tumor susceptibility role of AIP and CDKN1B/p27Kip1 in endocrine neoplasia. Clarifying the PAP phenotype facilitates the identification of potential AIP mutation carriers. Genetic counseling can be offered to the relatives and follow-up of the mutation carriers can be organized, hence an earlier diagnosis is feasible.

Framing as status or benefits? Consumers’ reactions to hierarchical loyalty program communication

Purpose A fundamental aspect of hierarchical loyalty programs is that some consumers get rewards that others do not. Despite the widespread use of such programs, academics have long debated whether these benefits are outweighed by the potential negative impact of the differential treatment of customers. This study extends our understanding, examining the impact of message framing on consumers’ reactions to hierarchical loyalty structures. Design/methodology/approach Three online studies were conducted. Study 1 uses advertisements to manipulate the message frame’s emphasis (benefits vs. status). Study 2 manipulates consumers’ frame of thought by directing their attention to either changes in benefits or status. Finally, Study 3 uses the proposed framework to reconcile contradictory findings from past research. Findings Low-frequency customers who do not expect to qualify for a superior customer tier tend to reject hierarchical programs when thinking about status. In contrast, when these customers think about concrete rewards, loyalty program messages produce no negative reactions. High-frequency customers are positively affected by communication regardless of the type of benefits framed. Research limitations/implications All studies were done online potentially limiting the external validity of the results. Nevertheless, the impact of message framing on perceptions about the loyalty program seems to be quite robust across different studies and manipulations. Practical implications When communicating with low-frequency customers managers should avoid promising status; customers should instead be motivated based on concrete rewards. High-frequency customers are indifferent to alternative emphasis of communication frames. Originality/value Marketing academics have acknowledged the importance of being able to reward top customers without demotivating light and moderate users. Our research is the first to provide a solution to this issue.

"Gift Giving" by wild bottle-nose dolphins (tursiops sp.) to humans at a wild dolphin provisioning program, Tangalooma, Australia

Since 1992, wild dolphin provisioning has occurred on a nightly basis at Tangalooma, a resort located on Moreton Island, Australia. Each evening at dusk up to 12 bottlenose dolphins (Tursiops sp.) are provided with fish in a regulated provisioning program. Since July 1998, biologists managing the program have documented 23 occurrences of "gift giving," when several of the provisioned dolphins have offered wild-caught cephalopod or fin fish species to staff members. The characteristics of each of these events are presented, and we explore the relationships between these events and their temporal patterns, and the age and sex of the dolphins involved. We also consider the behavioral explanations for the "gift giving," including prey sharing, play, and teaching behaviors, which have previously been described for cetaceans and other higher mammals. Gift giving may occur either as a discreet behavior (that may be a sequel to one or more other behaviors such as play or food preparation), or as a part of other behaviors, such as play and/or food sharing. It is most likely a manifestation of the particular relationship between the provisioned dolphins and the human participants in the provisioning. Gift giving has become an established but infrequent part of the culture of the provisioned dolphins at Tangalooma. © ISAZ 2012 Printed in the UK.

Forward osmosis as a pre-treatment for treating coal seam gas associated water: Flux and fouling behaviours

In this study, a bench scale forward osmosis (FO) process was operated using two commonly available FO membranes in different orientations in order to examine the removal of foulants in the coal seam gas (CSG) associated water, the water flux and fouling behaviours of the process were also investigated. After 48 h of fouling simulation experiment, the water flux declined by approximately 55 and 35% of its initial level in the TFC-PRO and CTA-PRO modes (support layer facing the feed), respectively, while the flux decline in the TFC-FO and CTA-FO modes (active layer facing the feed) was insignificant. The flux decline in PRO modes was caused by the compounding effects of internal concentration polarisation and membrane fouling. However, the declined flux was completely recovered to its initial level following the hydraulic cleaning using deionised water. Dissolved organic carbon (DOC), adenosine tri-phosphate (ATP) and major inorganic scalants (Ca, Mg and silica) in the CSG feed were effectively removed by using the FO process. The results of this study suggest that the FO process shows promising potential to be employed as an effective pre-treatment for membrane purification of CSG associated water.

The influence of pre- and post-zygotic barriers on interspecific Corymbia hybridization

Corymbia species from different sections hybridize readily, with some of increasing economic importance to plantation forestry. This study explores the locations of reproductive barriers between interspecific Corymbia hybrids and investigates the reproductive success of a wide taxonomic range of C. torelliana hybrid crosses. Pollen, pistil and embryo development were investigated for four C. torelliana crosses (C. torelliana, C. citriodora subsp. citriodora, C. tessellaris and C. intermedia) using fluorescent and standard microscopy to identify the locations of interspecific reproductive isolating barriers. Corymbia torelliana was also crossed with 16 taxa, representing six of the seven Corymbia sections, both Corymbia subgenera and one species each from the related genera, Angophora and Eucalyptus. All crosses were assessed for capsule and seed yields. Interspecific C. torelliana hybridization was controlled by pre-zygotic reproductive isolating barriers inhibiting pollen adhesion to the stigma, pollen germination, pollen tube growth in the style and pollen tube penetration of the micropyle. Corymbia torelliana (subgenus Blakella, sect. Torellianae) was successfully hybridized with Corymbia species from subgenus Blakella, particularly C. citriodora subsp. citriodora, C. citriodora subsp. variegata, C. henryi (sect. Maculatae) and C. tessellaris (sect. Abbreviatae), and subgenus Corymbia, particularly C. clarksoniana and C. erythrophloia (sect. Septentrionales). Attempted intergeneric hybrids between C. torelliana and either Angophora floribunda or Eucalyptus pellita were unsuccessful. Corymbia hybrids were formed between species from different sections and subgenera, but not with species from the related genera Angophora or Eucalyptus. Reproductive isolation between the interspecific Corymbia hybrid crosses was controlled by early- and late-acting pre-zygotic isolating barriers, with reproductive success generally decreasing with increasing taxonomic distance between parent species. These findings support the monophyly of Corymbia and the close relationships of infrageneric clades. The hybridizing propensity of Corymbia species provides opportunities for breeding but suggests risks of environmental gene flow. © The Author 2012. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Integrated disease management of stem end rot of mango in the Southern Philippines

This research aimed to develop and evaluate pre- and postharvest management strategies to reduce stem end rot (SER) incidence and extend saleable life of 'Carabao' mango fruits in Southern Philippines. Preharvest management focused on the development and improvement of fungicide spray program, while postharvest management aimed to develop alternative interventions aside from hot water treatment (HWT). Field evaluation of systemic fungicides, namely azoxystrobin ( Amistar 25SC), tebuconazole ( Folicur 25WP), carbendazim ( Goldazim 500SC), difenoconazole ( Score 250SC) and azoxystrobin+difenoconazole ( Amistar Top), reduced blossom blight severity and improved fruit setting and retention, resulting in higher fruit yield but failed to sufficiently suppress SER incidence. Based on these findings, an improved fungicide spray program was developed taking into account the infection process of SER pathogens and fungicide resistance. Timely application of protectant (mancozeb) and systemic fungicides (azoxystrobin, carbendazim and difenoconazole) during the most critical stages of mango flower and fruit development ensured higher harvestable fruit yield and minimally lowered SER incidence. Control of SER was also achieved by employing postharvest treatment such as HWT (52-55°C for 10 min), which significantly prolonged the saleable life of mango fruits. However, extended hot water treatment (EHWT; 46°C pulp temperature for 15 min), rapid heat treatment (RHT; 59°C for 30-60 sec), fungicide dip and promising biological control agents failed to satisfactorily reduce SER and prolong saleable life. In contrast, the integration of the improved spray program as preharvest management practice, and postharvest treatments such as HWT and fungicide dips (azoxystrobin, 150-175 ppm; carbendazim, 312.5 ppm; and tebuconazole, 125-156 ppm), significantly reduced disease and extended marketable life for utmost 8 days.

The short-term effects of a routine poisoning campaign on the movements and detectability of a social top-predator

Top-predators can be important components of resilient ecosystems, but they are still controlled in many places to mitigate a variety of economic, environmental and/or social impacts. Lethal control is often achieved through the broad-scale application of poisoned baits. Understanding the direct and indirect effects of such lethal control on subsequent movements and behaviour of survivors is an important pre-requisite for interpreting the efficacy and ecological outcomes of top-predator control. In this study, we use GPS tracking collars to investigate the fine-scale and short-term movements of dingoes (Canis lupus dingo and other wild dogs) in response to a routine poison-baiting program as an example of how a common, social top-predator can respond (behaviourally) to moderate levels of population reduction. We found no consistent control-induced differences in home range size or location, daily distance travelled, speed of travel, temporal activity patterns or road/trail usage for the seven surviving dingoes we monitored immediately before and after a typical lethal control event. These data suggest that the spatial behaviour of surviving dingoes was not altered in ways likely to affect their detectability, and if control-induced changes in dingoes' ecological function did occur, these may not be related to altered spatial behaviour or movement patterns.

Exercise and vascular function in child obesity: A meta-analysis

CONTEXT: Conduit artery flow-mediated dilation (FMD) is a noninvasive index of preclinical atherosclerosis in humans. Exercise interventions can improve FMD in both healthy and clinical populations. OBJECTIVE: This systematic review and meta-analysis aimed to summarize the effect of exercise training on FMD in overweight and obese children and adolescents as well as investigate the role of cardiorespiratory fitness (peak oxygen consumption [Vo2peak]) on effects observed. DATA SOURCES: PubMed, Medline, Embase, and Cinahl databases were searched from the earliest available date to February 2015. STUDY SELECTION: Studies of children and/or adolescents who were overweight or obese were included. DATA EXTRACTION: Standardized data extraction forms were used for patient and intervention characteristics, control/comparator groups, and key outcomes. Procedural quality of the studies was assessed using a modified version of the Physiotherapy Evidence Base Database scale. RESULTS: A meta-analysis involving 219 participants compared the mean difference of pre- versus postintervention vascular function (FMD) and Vo2peak between an exercise training intervention and a control condition. There was a significantly greater improvement in FMD (mean difference 1.54%, P < .05) and Vo2peak (mean difference 3.64 mL/kg/min, P < .05) after exercise training compared with controls. LIMITATIONS: Given the diversity of exercise prescriptions, participant characteristics, and FMD measurement protocols, varying FMD effect size was noted between trials. CONCLUSIONS: Exercise training improves vascular function in overweight and obese children, as indicated by enhanced FMD. Further research is required to establish the optimum exercise program for maintenance of healthy vascular function in this at-risk pediatric population.

Drink driving among Indigenous Australians in outer regional and remote communities and development of a drink driving program: A summary of findings and recommendations

Drink driving is a leading cause of criminal justice system contact for Indigenous Australians. National and state strategies recommend Indigenous road safety initiatives are warranted. However, there is sparse evidence to inform drink driving-related preventive and treatment measures. Using quantitative and qualitative methods, the study examines the profile of Queensland’s Indigenous drink drivers using court convictions and identifies the contributing psycho-social, cultural and contextual factors through qualitative interviews.

Emotional climate of a pre-service science teacher education class in Bhutan

This study explored pre-service secondary science teachers’ perceptions of classroom emotional climate in the context of the Bhutanese macro-social policy of Gross National Happiness. Drawing upon sociological perspectives of human emotions and using Interaction Ritual Theory this study investigated how pre-service science teachers may be supported in their professional development. It was a multi-method study involving video and audio recordings of teaching episodes supported by interviews and the researcher’s diary. Students also registered their perceptions of the emotional climate of their classroom at 3-minute intervals using audience response technology. In this way, emotional events were identified for video analysis. The findings of this study highlighted that the activities pre-service teachers engaged in matter to them. Positive emotional climate was identified in activities involving students’ presentations using video clips and models, coteaching, and interactive whole class discussions. Decreases in emotional climate were identified during formal lectures and when unprepared presenters led presentations. Emotions such as frustration and disappointment characterized classes with negative emotional climate. The enabling conditions to sustain a positive emotional climate are identified. Implications for sustaining macro-social policy about Gross National Happiness are considered in light of the climate that develops in science teacher education classes.