Perceiving animacy from shape

Superordinate visual classification—for example, identifying an image as “animal,” “plant,” or “mineral”—is computationally challenging because radically different items (e.g., “octopus,” “dog”) must be grouped into a common class (“animal”). It is plausible that learning superordinate categories teaches us not only the membership of particular (familiar) items, but also general features that are shared across class members, aiding us in classifying novel (unfamiliar) items. Here, we investigated visual shape features associated with animate and inanimate classes. One group of participants viewed images of 75 unfamiliar and atypical items and provided separate ratings of how much each image looked like an animal, plant, and mineral. Results show systematic tradeoffs between the ratings, indicating a class-like organization of items. A second group rated each image in terms of 22 midlevel shape features (e.g., “symmetrical,” “curved”). The results confirm that superordinate classes are associated with particular shape features (e.g., “animals” generally have high “symmetry” ratings). Moreover, linear discriminant analysis based on the 22-D feature vectors predicts the perceived classes approximately as well as the ground truth classification. This suggests that a generic set of midlevel visual shape features forms the basis for superordinate classification of novel objects along the animacy continuum

A stringent yeast two-hybrid matrix screening approach for protein-protein interaction discovery

The yeast two-hybrid (Y2H) system is currently one of the most important techniques for protein-protein interaction (PPI) discovery. Here, we describe a stringent three-step Y2H matrix interaction approach that is suitable for systematic PPI screening on a proteome scale. We start with the identification and elimination of autoactivating strains that would lead to false-positive signals and prevent the identification of interactions. Nonautoactivating strains are used for the primary PPI screen that is carried out in quadruplicate with arrayed preys. Interacting pairs of baits and preys are identified in a pairwise retest step. Only PPI pairs that pass the retest step are regarded as potentially biologically relevant interactions and are considered for further analysis

TOT Approach in stress urinary incontinence (SUI) – outcome in obese female

BACKGROUND: Only limited data are available on the outcome of tension-free obturator tape (TOT) procedures in overweight and obese women. We would like to verify the objective and subjective outcomes of TOT in women with a higher body mass index (BMI). METHODS: We evaluated the records of 116 patients who had undergone TOT, stratifying by BMI into normal weight (n = 31), overweight (n = 56), and obese (n = 29) groups. We compared pre- and postoperative evaluations, including subjective and objective outcome of TOT, complications, and quality of life assessed by validated questionnaires (ICIQ-SF and KHQ). RESULTS: The median follow-up was 21 months. There were no significant differences between different groups in terms of objective cure rate and subjective success, quality of life scores and postoperative complications. CONCLUSIONS: Our data demonstrate that TOT procedure is safe and effective. BMI did not influence the outcome of TOT procedures at a median of 21 months after surgery and represents no contraindication for continence surgery. The success of the outcome of TOT procedure in females and the occurrence of complications are not negatively affected by obesity

Procedurally reducing complexity: the practices of German EU policy coordination

"Policy coordination in federal states is inherently complex because it includes a multitude of actors at the federal and the sub-state level. If the sub-states want their interests to be included in the final decision, they need to coordinate with the federal level but also amongst themselves. Several individual interests are overlooked easier than coordinated interests of a group of sub-states. This paper puts forward the argument that during the coordination process, the actors from both levels meet in different constellations where they focus on different aspects of coordination, especially on different actors' interests separately. This is a strategy which enables them to procedurally reduce the complexity of the decision-making process. In order to empirically investigate this argument, first a thorough definition of coordination as process is provided and operationalized for empirical investigation. It is accentuated that coordination as a process has different dimensions which are relevant for the understanding of the coordination process. This argument is analyzed with the example case of German EU policy. The empirical data used are original expert interviews with German civil servants responsible for EU policy coordination at the sub-state level. It will be demonstrated that the actors strategically form voluntary coordination constellations which enables them to reduce complexity during the process." (author's abstract

BRCA2 variants and cardiovascular disease in a multi-ethnic study.

BACKGROUND: Germline mutations of BRCA1/2 are associated with hereditary breast and ovarian cancer. Recent data suggests excess mortality in mutation carriers beyond that conferred by neoplasia, and recent in vivo and in vitro studies suggest a modulatory role for BRCA proteins in endothelial and cardiomyocyte function. We therefore tested the association of BRCA2 variants with clinical cardiovascular disease (CVD). METHODS: Using data from 1,170 individuals included in two multi-ethnic population-based studies (SHARE and SHARE-AP), the association between BRCA2 variants and CVD was evaluated. 15 SNPs in BRCA2 with minor allele frequencies (MAF) > 0.01 had been previously genotyped using the cardiovascular gene-centric 50 k SNP array. 115 individuals (9.8%) reported a CVD event, defined as myocardial infarction (MI), angina, silent MI, stroke, and angioplasty or coronary artery bypass surgery. Analyses were adjusted for age and sex. The SNPs rs11571836 and rs1799943 were subsequently genotyped using the MassARRAY platform in 1,045 cases of incident MI and 1,135 controls from the South Asian subset of an international case-control study of acute MI (INTERHEART), and rs11571836 was imputed in 4,686 cases and 4500 controls from the Pakistan Risk of Myocardial Infarction Study (PROMIS). RESULTS: Two BRCA2 SNPs, rs11571836 and rs1799943, both located in untranslated regions, were associated with lower risk of CVD (OR 0.47 p = 0.01 and OR 0.56 p = 0.03 respectively) in the SHARE studies. Analysis by specific ethnicities demonstrated an association with CVD for both SNPs in Aboriginal People, and for rs11571836 only in South Asians. No association was observed in the European and Chinese subgroups. A non-significant trend towards an association between rs11571836 and lower risk of MI was observed in South Asians from INTERHEART [OR = 0.87 (95% CI: 0.75-1.01) p = 0.068], but was not evident in PROMIS [OR = 0.96 (95% CI: 0.90-1.03) p = 0.230]. Meta-analysis of both case-control studies resulted in a combined OR of 0.94 (95% CI: 0.89-1.004, p = 0.06). CONCLUSIONS: Although there was an association between two SNPs in BRCA2 and CVD in a multi-ethnic population, these results were not replicated in two South Asian case-control studies of incident MI. Future studies exploring the association between BRCA variants and cardiovascular disorders are needed to clarify the role, if any, for BRCA variants in CVD pathogenesis.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Peroxisomal proliferator activated receptor-γ deficiency in a Canadian kindred with familial partial lipodystrophy type 3 (FPLD3)

BACKGROUND: Familial partial lipodystrophy (Dunnigan) type 3 (FPLD3, Mendelian Inheritance in Man [MIM] 604367) results from heterozygous mutations in PPARG encoding peroxisomal proliferator-activated receptor-γ. Both dominant-negative and haploinsufficiency mechanisms have been suggested for this condition. METHODS: We present a Canadian FPLD3 kindred with an affected mother who had loss of fat on arms and legs, but no increase in facial, neck, suprascapular or abdominal fat. She had profound insulin resistance, diabetes, severe hypertriglyceridemia and relapsing pancreatitis, while her pre-pubescent daughter had normal fat distribution but elevated plasma triglycerides and C-peptide and depressed high-density lipoprotein cholesterol. RESULTS: The mother and daughter were each heterozygous for PPARG nonsense mutation Y355X, whose protein product in vitro was transcriptionally inactive with no dominant-negative activity against the wild-type receptor. In addition the mutant protein appeared to be markedly unstable. CONCLUSION: Taken together with previous studies of human PPARG mutations, these findings suggest that PPAR-γ deficiency due either to haploinsufficiency or to substantial activity loss due to dominant negative interference of the normal allele product's function can each contribute to the FPLD3 phenotype

Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society

AIMS: Homozygous familial hypercholesterolaemia (HoFH) is a rare life-threatening condition characterized by markedly elevated circulating levels of low-density lipoprotein cholesterol (LDL-C) and accelerated, premature atherosclerotic cardiovascular disease (ACVD). Given recent insights into the heterogeneity of genetic defects and clinical phenotype of HoFH, and the availability of new therapeutic options, this Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society (EAS) critically reviewed available data with the aim of providing clinical guidance for the recognition and management of HoFH. METHODS AND RESULTS: Early diagnosis of HoFH and prompt initiation of diet and lipid-lowering therapy are critical. Genetic testing may provide a definitive diagnosis, but if unavailable, markedly elevated LDL-C levels together with cutaneous or tendon xanthomas before 10 years, or untreated elevated LDL-C levels consistent with heterozygous FH in both parents, are suggestive of HoFH. We recommend that patients with suspected HoFH are promptly referred to specialist centres for a comprehensive ACVD evaluation and clinical management. Lifestyle intervention and maximal statin therapy are the mainstays of treatment, ideally started in the first year of life or at an initial diagnosis, often with ezetimibe and other lipid-modifying therapy. As patients rarely achieve LDL-C targets, adjunctive lipoprotein apheresis is recommended where available, preferably started by age 5 and no later than 8 years. The number of therapeutic approaches has increased following approval of lomitapide and mipomersen for HoFH. Given the severity of ACVD, we recommend regular follow-up, including Doppler echocardiographic evaluation of the heart and aorta annually, stress testing and, if available, computed tomography coronary angiography every 5 years, or less if deemed necessary. CONCLUSION: This EAS Consensus Panel highlights the need for early identification of HoFH patients, prompt referral to specialized centres, and early initiation of appropriate treatment. These recommendations offer guidance for a wide spectrum of clinicians who are often the first to identify patients with suspected HoFH