Characterisation of the bacterial and fungal communities associated with different lesion sizes of Dark Spot Syndrome occurring in the Coral Stephanocoenia intersepta

The number and prevalence of coral diseases/syndromes are increasing worldwide. Dark Spot Syndrome (DSS) afflicts numerous coral species and is widespread throughout the Caribbean, yet there are no known causal agents. In this study we aimed to characterise the microbial communities (bacteria and fungi) associated with DSS lesions affecting the coral Stephanocoenia intersepta using nonculture molecular techniques. Bacterial diversity of healthy tissues (H), those in advance of the lesion interface (apparently healthy AH), and three sizes of disease lesions (small, medium, and large) varied significantly (ANOSIM R = 0.052 p,0.001), apart from the medium and large lesions, which were similar in their community profile. Four bacteria fitted into the pattern expected from potential pathogens; namely absent from H, increasing in abundance within AH, and dominant in the lesions themselves. These included ribotypes related to Corynebacterium (KC190237), Acinetobacter (KC190251), Parvularculaceae (KC19027), and Oscillatoria (KC190271). Furthermore, two Vibrio species, a genus including many proposed coral pathogens, dominated the disease lesion and were absent from H and AH tissues, making them candidates as potential pathogens for DSS. In contrast, other members of bacteria from the same genus, such as V. harveyii were present throughout all sample types, supporting previous studies where potential coral pathogens exist in healthy tissues. Fungal diversity varied significantly as well, however the main difference between diseased and healthy tissues was the dominance of one ribotype, closely related to the plant pathogen, Rhytisma acerinum, a known causal agent of tar spot on tree leaves. As the corals’ symbiotic algae have been shown to turn to a darker pigmented state in DSS (giving rise to the syndromes name), the two most likely pathogens are R. acerinum and the bacterium Oscillatoria, which has been identified as the causal agent of the colouration in Black Band Disease, another widespread coral disease

Phase I pharmacokinetic and pharmacodynamic study of the prenyl transferase inhibitor AZD3409 in patients with advanced cancer

AZD3409 is an orally active double prodrug that was developed as a novel dual prenyltransferase inhibitor. The formation of the active metabolite AZD3409 acid is mediated by esterases in plasma and cells. The aim of this phase I study was to determine the maximum tolerated dose, toxicities, pharmacokinetics and pharmacodynamics of AZD3409. AZD3409 was administered orally to patients with advanced solid malignancies using an interpatient dose-escalation scheme starting at 500 mg AZD3409 once daily. Twenty-nine patients were treated at seven dose levels. The MTD of part A was defined as 750 mg b.i.d. in the fasted state. Adverse events were mainly gastrointestinal and the severity was on average mild to moderate and reversible. The dose-limiting toxicities were vomiting, diarrhoea and uncontrolled nausea. Pharmacokinetic studies of the prodrug and the active metabolite indicated dose proportionality. Pharmacodynamic studies showed that farnesyltransferase (FTase) was inhibited at all dose levels. In conclusion, chronic oral dosing with AZD3409 is feasible and results in significant inhibition of FTase activity. Pharmacodynamic studies revealed that the maximal FTase inhibition, estimated at 49±11%, appeared to be reached at AZD3409 acid plasma concentrations at which the occurrence of drug-related toxicity was low. This study supports the rationale to implement biological effect studies in clinical trials with biologically active anticancer drugs to define optimal dosing regimens

Mimicry of Food Intake: The Dynamic Interplay between Eating Companions

Numerous studies have shown that people adjust their intake directly to that of their eating companions; they eat more when others eat more, and less when others inhibit intake. A potential explanation for this modeling effect is that both eating companions' food intake becomes synchronized through processes of behavioral mimicry. No study, however, has tested whether behavioral mimicry can partially account for this modeling effect. To capture behavioral mimicry, real-time observations of dyads of young females having an evening meal were conducted. It was assessed whether mimicry depended on the time of the interaction and on the person who took the bite. A total of 70 young female dyads took part in the study, from which the total number of bites (N = 3,888) was used as unit of analyses. For each dyad, the total number of bites and the exact time at which each person took a bite were coded. Behavioral mimicry was operationalized as a bite taken within a fixed 5-second interval after the other person had taken a bite, whereas non-mimicked bites were defined as bites taken outside the 5-second interval. It was found that both women mimicked each other's eating behavior. They were more likely to take a bite of their meal in congruence with their eating companion rather than eating at their own pace. This behavioral mimicry was found to be more prominent at the beginning than at the end of the interaction. This study suggests that behavioral mimicry may partially account for social modeling of food intake

Comparison of the fracture resistance of endodontically treated teeth restored with prefabricated posts and composite resin cores with different post lenghts

OBJECTIVE: This study evaluated the fracture strengths of endodontically treated teeth restored with prefabricated posts with different post lengths. MATERIAL AND METHODS: Thirty freshly extracted canines were endodontically treated. They were randomly divided into groups of 10 teeth and prepared according to 3 experimental protocols, as follows; Group 1/3 PP: teeth restored with prefabricated post and composite resin core (Z250) with post length of 5.0mm; Group 1/2 PP and Group 2/3 PP: teeth restored with prefabricated post and composite resin core (Z250) with different combinations of post length of 7.5mm and 10mm, respectively. All teeth were restored with full metal crowns. The fracture resistance (N) was measured in a universal testing machine (crosshead speed 0.5mm/min) at 45 degrees to the tooth long axis until failure. Data were analyzed by one-way analysis of variance (alpha=.05). RESULTS: The one-way analysis of variance demonstrated no significant difference among the different post lengths (P>;.05) (Groups 1/3 PP = 405.4 N, 1/2 PP = 395.6 N, 2/3 PP = 393.8 N). Failures occurred mainly due to core fracture. CONCLUSIONS: The results of this study showed that an increased post length in teeth restored with prefabricated posts did not significantly increase the fracture resistance of endodontically treated teeth

Interspecific Hybridization Increased in Congeneric Flatfishes after the Prestige Oil Spill

Marine species with relatively low migratory capacity are threatened by habitat alterations derived from human activities. In November 2002 the tanker Prestige sank off the Spanish northwest coast releasing 70,000 tons of fuel and damaging biota in the area. Despite efforts to clean the damaged areas, fuel remnants have affected marine species over the last nine years. This study is focused on two flatfish, Lepidorhombus boscii (four-spotted megrim) and L. whiffiagonis (megrim), whose spawning areas are located at the edge of the continental platform. We have analyzed megrim samples from North Spanish and French waters obtained before and after the oil spill. Genotypes at the nuclear marker 5S rDNA indicate a significant increase in interspecific hybridization after the Prestige accident, likely due to forced spawning overlap. The mitochondrial D-Loop region was employed for determining the direction of hybrid crosses, which were most frequently L. boscii female x L. whiffiagonis male. Reduced ability of L. boscii females to select conspecific mates would explain such asymmetric hybridization. To our knowledge this is the first time that increased hybridization between fish species can be associated to an oil spill. These results illustrate the potential long-term effect of petrol wastes on wild fish species

Analysis of the Mitogen-activated protein kinase kinase 4 (MAP2K4) tumor suppressor gene in ovarian cancer

<p>Abstract</p> <p>Background</p> <p><it>MAP2K4 </it>is a putative tumor and metastasis suppressor gene frequently found to be deleted in various cancer types. We aimed to conduct a comprehensive analysis of this gene to assess its involvement in ovarian cancer.</p> <p>Methods</p> <p>We screened for mutations in <it>MAP2K4 </it>using High Resolution Melt analysis of 149 primary ovarian tumors and methylation at the promoter using Methylation-Specific Single-Stranded Conformation Polymorphism analysis of 39 tumors. We also considered the clinical impact of changes in <it>MAP2K4 </it>using publicly available expression and copy number array data. Finally, we used siRNA to measure the effect of reducing <it>MAP2K4 </it>expression in cell lines.</p> <p>Results</p> <p>In addition to 4 previously detected homozygous deletions, we identified a homozygous 16 bp truncating deletion and a heterozygous 4 bp deletion, each in one ovarian tumor. No promoter methylation was detected. The frequency of <it>MAP2K4 </it>homozygous inactivation was 5.6% overall, and 9.8% in high-grade serous cases. Hemizygous deletion of <it>MAP2K4 </it>was observed in 38% of samples. There were significant correlations of copy number and expression in three microarray data sets. There was a significant correlation between <it>MAP2K4 </it>expression and overall survival in one expression array data set, but this was not confirmed in an independent set. Treatment of JAM and HOSE6.3 cell lines with <it>MAP2K4 </it>siRNA showed some reduction in proliferation.</p> <p>Conclusions</p> <p><it>MAP2K4 </it>is targeted by genetic inactivation in ovarian cancer and restricted to high grade serous and endometrioid carcinomas in our cohort.</p

On ethically solvent leaders : the roles of pride and moral identity in predicting leader ethical behavior.

The popular media has repeatedly pointed to pride as one of the key factors motivating leaders to behave unethically. However, given the devastating consequences that leader unethical behavior may have, a more scientific account of the role of pride is warranted. The present study differentiates between authentic and hubristic pride and assesses its impact on leader ethical behavior, while taking into consideration the extent to which leaders find it important to their self-concept to be a moral person. In two experiments we found that with higher levels of moral identity, authentically proud leaders are more likely to engage in ethical behavior than hubristically proud leaders, and that this effect is mediated by leaders’ motivation to act selflessly. A field survey among organizational leaders corroborated that moral identity may bring the positive effect of authentic pride and the negative effect of hubristic pride on leader ethical behavior to the forefront

Embodying compassion: A virtual reality paradigm for overcoming excessive self-criticism

Virtual reality has been successfully used to study and treat psychological disorders such as phobias and posttraumatic stress disorder but has rarely been applied to clinically-relevant emotions other than fear and anxiety. Self-criticism is a ubiquitous feature of psychopathology and can be treated by increasing levels of self-compassion. We exploited the known effects of identification with a virtual body to arrange for healthy female volunteers high in self-criticism to experience self-compassion from an embodied first-person perspective within immersive virtual reality. Whereas observation and practice of compassionate responses reduced self-criticism, the additional experience of embodiment also increased self-compassion and feelings of being safe. The results suggest potential new uses for immersive virtual reality in a range of clinical conditions.N/

Resolving the paradox of shame: differentiating among specific appraisal-feeling combinations explains pro-social and self-defensive motivation

Research has shown that people can respond both self-defensively and pro-socially when they experience shame. We address this paradox by differentiating among specific appraisals (of specific self-defect and concern for condemnation) and feelings (of shame, inferiority, and rejection) often reported as part of shame. In two Experiments (Study 1: N = 85; Study 2: N = 112), manipulations that put participants’ social-image at risk increased their appraisal of concern for condemnation. In Study 2, a manipulation of moral failure increased participants’ appraisal that they suffered a specific self-defect. In both studies, mediation analyses showed that effects of the social-image at risk manipulation on self-defensive motivation were explained by appraisal of concern for condemnation and felt rejection. In contrast, the effect of the moral failure manipulation on pro-social motivation in Study 2 was explained by appraisal of a specific self-defect and felt shame. Thus, distinguishing among the appraisals and feelings tied to shame enabled clearer prediction of pro-social and self-defensive responses to moral failure with and without risk to social-image

Frequency of the ATM IVS10-6T→G variant in Australian multiple-case breast cancer families

BACKGROUND: Germline mutations in the genes BRCA1 and BRCA2 account for only a proportion of hereditary breast cancer, suggesting that additional genes contribute to hereditary breast cancer. Recently a heterozygous variant in the ataxia–telangiectasia mutated (ATM) gene, IVS10-6T→G, was reported by an Australian multiple-case breast cancer family cohort study (the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer) to confer a substantial breast cancer risk. Although this variant can result in a truncated ATM product, its clinical significance as a high-penetrance breast cancer allele or its role as a low-penetrance risk-modifier is controversial. METHODS: We determined the frequency of ATM IVS10-6T→G variants in a cohort of individuals affected by breast and/or ovarian cancer who underwent BRCA1 and BRCA2 genetic testing at four major Australian familial cancer clinics. RESULTS: Seven of 495 patients (1.4%) were heterozygous for the IVS10-6T→G variant; the carrier rate in unselected Australian women with no family history of breast cancer is reported to be 6 of 725 (0.83%) (P = 0.4). Two of the seven probands also harboured a pathogenic BRCA1 mutation and one patient had a BRCA1 unclassified variant of uncertain significance. CONCLUSION: These findings indicate that the ATM IVS10-6T→G variant does not seem to occur at a significantly higher frequency in affected individuals from high-risk families than in the general population. A role for this variant as a low-penetrance allele or as a modifying gene in association with other genes (such as BRCA1) remains possible. Routine testing for ATM IVS10-6T→G is not warranted in mutation screening of affected individuals from high-risk families