Genetic profile in patients with complicated acute aortic syndrome: the GEN-AOR study.

INTRODUCTION AND OBJECTIVES: Genetic testing is becoming increasingly important for diagnosis and personalized treatments in aortopathies. Here, we aimed to genetically diagnose a group of acute aortic syndrome (AAS) patients consecutively admitted to an intensive care unit and to explore the clinical usefulness of AAS-associated variants during treatment decision-making and family traceability. METHODS: We applied targeted next-generation sequencing, covering 42 aortic diseases genes in AAS patients with no signs consistent with syndromic conditions. Detected variants were segregated by Sanger sequencing in available family members. Demographic features, risk factors and clinical symptoms were statistically analyzed by Fisher or Fisher-Freeman-Halton Exact tests, to assess their relationship with genetic results. RESULTS: Analysis of next-generation sequencing data in 73 AAS patients led to the detection of 34 heterozygous candidate variants in 14 different genes in 32 patients. Family screening was performed in 31 relatives belonging to 9 families. We found 13 relatives harboring the family variant, of which 10 showed a genotype compatible with the occurrence of AAS. Statistical tests revealed that the factors associated with a positive genetic diagnosis were the absence of hypertension, lower age, family history of AAS and absence of pain. CONCLUSIONS: Our findings broaden the spectrum of the genetic background for AAS. In addition, both index patients and studied relatives benefited from the results obtained, establishing the most appropriate level of surveillance for each group. Finally, this strategy could be reinforced by the use of stastistically significant clinical features as a predictive tool for the hereditary character of AAS. CLINICALTRIALS: gov (Identifier: NCT04751058).

Assessing restricted stimulus control in typically developing preschool children and bees (Melipona quadrifasciata)

This study established a simple simultaneous discrimination between a pair of two-element compound visual stimuli in children (Experiment 1) and bees (Melipona quadrifasciata, Experiment 2). The contingencies required discriminative control by the compound and the question was whether the accurate stimulus control reached at this level would hold for each individual element of the compound. After baseline reached stability, probe trials assessed stimulus control by each single element of both S+ and S-. Average data showed that children (Exp. 1) tended to show stimulus control by a single element of the S+ compound. In Experiment 2 three of four bees showed stimulus control by both elements of S+ and did not respond or responded only infrequently to the elements of the S-. The children's decline in discrimination accuracy in probe trials, along with its maintenance during the baseline, replicated previous findings showing the development of restricted stimulus control (RSC). The precise stimulus control shown by the bees indicated that all elements correlated with reinforcement acquired stimulus control over their behavior; this confirms the extensive literature on visual discriminative learning in bees, but due to the small number of subjects it is premature to say that bees do not develop RSC...

Assessing restricted stimulus control in typically developing preschool children and bees (Melipona quadrifasciata)

This study established a simple simultaneous discrimination between a pair of two-element compound visual stimuli in children (Experiment 1) and bees (Melipona quadrifasciata, Experiment 2). The contingencies required discriminative control by the compound and the question was whether the accurate stimulus control reached at this level would hold for each individual element of the compound. After baseline reached stability, probe trials assessed stimulus control by each single element of both S+ and S-. Average data showed that children (Exp. 1) tended to show stimulus control by a single element of the S+ compound. In Experiment 2 three of four bees showed stimulus control by both elements of S+ and did not respond or responded only infrequently to the elements of the S-. The children's decline in discrimination accuracy in probe trials, along with its maintenance during the baseline, replicated previous findings showing the development of restricted stimulus control (RSC). The precise stimulus control shown by the bees indicated that all elements correlated with reinforcement acquired stimulus control over their behavior; this confirms the extensive literature on visual discriminative learning in bees, but due to the small number of subjects it is premature to say that bees do not develop RSC.(AU)

Dimethylaminopyridine derivatives of lupane triterpenoids cause mitochondrial disruption and induce the permeability transition.

Triterpenoids are a large class of naturally occurring compounds, and some potentially interesting as anticancer agents have been found to target mitochondria. The objective of the present work was to investigate the mechanisms of mitochondrial toxicity induced by novel dimethylaminopyridine (DMAP) derivatives of pentacyclic triterpenes, which were previously shown to inhibit the growth of melanoma cells in vitro. MCF-7, Hs 578T and BJ cell lines, as well as isolated hepatic mitochondria, were used to investigate direct mitochondrial effects. On isolated mitochondrial hepatic fractions, respiratory parameters, mitochondrial transmembrane electric potential, induction of the mitochondrial permeability transition (MPT) pore and ion transport-dependent osmotic swelling were measured. Our results indicate that the DMAP triterpenoid derivatives lead to fragmentation and depolarization of the mitochondrial network in situ, and to inhibition of uncoupled respiration, induction of the permeability transition pore and depolarization of isolated hepatic mitochondria. The results show that mitochondrial toxicity is an important component of the biological interaction of DMAP derivatives, which can explain the effects observed in cancer cells.

Honeybees can discriminate between Monet and Picasso paintings.

Honeybees (Apis mellifera) have remarkable visual learning and discrimination abilities that extend beyond learning simple colours, shapes or patterns. They can discriminate landscape scenes, types of flowers, and even human faces. This suggests that in spite of their small brain, honeybees have a highly developed capacity for processing complex visual information, comparable in many respects to vertebrates. Here, we investigated whether this capacity extends to complex images that humans distinguish on the basis of artistic style: Impressionist paintings by Monet and Cubist paintings by Picasso. We show that honeybees learned to simultaneously discriminate between five different Monet and Picasso paintings, and that they do not rely on luminance, colour, or spatial frequency information for discrimination. When presented with novel paintings of the same style, the bees even demonstrated some ability to generalize. This suggests that honeybees are able to discriminate Monet paintings from Picasso ones by extracting and learning the characteristic visual information inherent in each painting style. Our study further suggests that discrimination of artistic styles is not a higher cognitive function that is unique to humans, but simply due to the capacity of animals-from insects to humans-to extract and categorize the visual characteristics of complex images.

Increased vulnerability of brain mitochondria in diabetic (Goto-Kakizaki) rats with aging and amyloid-beta exposure.

This study evaluated the respiratory indexes (respiratory control ratio [RCR] and ADP/O ratio), mitochondrial transmembrane potential (DeltaPsim), repolarization lag phase, repolarization level, ATP/ADP ratio, and induction of the permeability transition pore of brain mitochondria isolated from normal Wistar and GK diabetic rats of different ages (1.5, 12, and 24 months of age). The effect of amyloid beta-peptides, 50 micromol/l Abeta(25-35) or 2 micromol/l Abeta(1-40), on mitochondrial function was also analyzed. Aging of diabetic mice induced a decrease in brain mitochondrial RCR, ADP/O, and ATP/ADP ratios but induced an increase in the repolarization lag phase. Brain mitochondria from older diabetic rats were more prone to the induction of the permeability transition pore, i.e., mitochondria from 24-month-old diabetic rats accumulated much less Ca(2+) (20 micromol/l) than those isolated from 12-month-old rats (50 micromol/l) or 1.5-month-old rats (100 micromol/l). In the presence of 50 micromol/l Abeta(25-35) or 2 micromol/l Abeta(1-40), age-related mitochondrial effects were potentiated. These results indicate that diabetes-related mitochondrial dysfunction is exacerbated by aging and/or by the presence of neurotoxic agents such as amyloid beta-peptides, supporting the idea that diabetes and aging are risk factors for the neurodegeneration induced by these peptides.