Intrinsic activity in the fly brain gates visual information during behavioral choices

The small insect brain is often described as an input/output system that executes reflex-like behaviors. It can also initiate neural activity and behaviors intrinsically, seen as spontaneous behaviors, different arousal states and sleep. However, less is known about how intrinsic activity in neural circuits affects sensory information processing in the insect brain and variability in behavior. Here, by simultaneously monitoring Drosophila's behavioral choices and brain activity in a flight simulator system, we identify intrinsic activity that is associated with the act of selecting between visual stimuli. We recorded neural output (multiunit action potentials and local field potentials) in the left and right optic lobes of a tethered flying Drosophila, while its attempts to follow visual motion (yaw torque) were measured by a torque meter. We show that when facing competing motion stimuli on its left and right, Drosophila typically generate large torque responses that flip from side to side. The delayed onset (0.1-1 s) and spontaneous switch-like dynamics of these responses, and the fact that the flies sometimes oppose the stimuli by flying straight, make this behavior different from the classic steering reflexes. Drosophila, thus, seem to choose one stimulus at a time and attempt to rotate toward its direction. With this behavior, the neural output of the optic lobes alternates; being augmented on the side chosen for body rotation and suppressed on the opposite side, even though the visual input to the fly eyes stays the same. Thus, the flow of information from the fly eyes is gated intrinsically. Such modulation can be noise-induced or intentional; with one possibility being that the fly brain highlights chosen information while ignoring the irrelevant, similar to what we know to occur in higher animals

The cohesive band model: A cohesive surface formulation with stress triaxiality

In the cohesive surface model cohesive tractions are transmitted across a two-dimensional surface, which is embedded in a three-dimensional continuum. The relevant kinematic quantities are the local crack opening displacement and the crack sliding displacement, but there is no kinematic quantity that represents the stretching of the fracture plane. As a consequence, in-plane stresses are absent, and fracture phenomena as splitting cracks in concrete and masonry, or crazing in polymers, which are governed by stress triaxiality, cannot be represented properly. In this paper we extend the cohesive surface model to include in-plane kinematic quantities. Since the full strain tensor is now available, a three-dimensional stress state can be computed in a straightforward manner. The cohesive band model is regarded as a subgrid scale fracture model, which has a small, yet finite thickness at the subgrid scale, but can be considered as having a zero thickness in the discretisation method that is used at the macroscopic scale. The standard cohesive surface formulation is obtained when the cohesive band width goes to zero. In principle, any discretisation method that can capture a discontinuity can be used, but partition-of-unity based finite element methods and isogeometric finite element analysis seem to have an advantage since they can naturally incorporate the continuum mechanics. When using interface finite elements, traction oscillations that can occur prior to the opening of a cohesive crack, persist for the cohesive band model. Example calculations show that Poisson contraction influences the results, since there is a coupling between the crack opening and the in-plane normal strain in the cohesive band. This coupling holds promise for capturing a variety of fracture phenomena, such as delamination buckling and splitting cracks, that are difficult, if not impossible, to describe within a conventional cohesive surface model. © 2013 Springer Science+Business Media Dordrecht

Numerical modeling of the tension stiffening in reinforced concrete members via discontinuum models

[prova tipográfica]This study presents a numerical investigation on the fracture mechanism of tension stiffening phenomenon in reinforced concrete members. A novel approach using the discrete element method (DEM) is proposed, where three-dimensional randomly generated distinct polyhedral blocks are used, representing concrete and one-dimensional truss elements are utilized, representing steel reinforcements. Thus, an explicit representation of reinforced concrete members is achieved, and the mechanical behavior of the system is solved by integrating the equations of motion for each block using the central difference algorithm. The inter-block interactions are taken into consideration at each contact point with springs and cohesive frictional elements. Once the applied modeling strategy is validated, based on previously published experimental findings, a sensitivity analysis is performed for bond stiffness, cohesion strength, and the number of truss elements. Hence, valuable inferences are made regarding discontinuum analysis of reinforced concrete members, including concrete-steel interaction and their macro behavior. The results demonstrate that the proposed phenomenological modeling strategy successfully captures the concrete-steel interaction and provides an accurate estimation of the macro behavior

Resistance to caspase-8 and -9 fragments in a malignant pleural mesothelioma cell line with acquired cisplatin-resistance

Apoptotic cysteine–aspartate proteases (caspases) are essential for the progression and execution of apoptosis, and detection of caspase fragmentation or activity is often used as markers of apoptosis. Cisplatin (cis-diamminedichloroplatinum (II)) is a chemotherapeutic drug that is clinically used for the treatment of solid tumours. We compared a cisplatin-resistant pleural malignant mesothelioma cell line (P31res1.2) with its parental cell line (P31) regarding the consequences of in vitro acquired cisplatin-resistance on basal and cisplatin-induced (equitoxic and equiapoptotic cisplatin concentrations) caspase-3, -8 and -9 fragmentation and proteolytic activity. Acquisition of cisplatin-resistance resulted in basal fragmentation of caspase-8 and -9 without a concomitant increase in proteolytic activity, and there was an increased basal caspase-3/7 activity. Similarly, cisplatin-resistant non-small-cell lung cancer cells, H1299res, had increased caspase-3 and -9 content compared with the parental H1299 cells. In P31 cells, cisplatin exposure resulted in caspase-9-mediated caspase-3/7 activation, but in P31res1.2 cells the cisplatin-induced caspase-3/7 activation occurred before caspase-8 or -9 activation. We therefore concluded that in vitro acquisition of cisplatin-resistance rendered P31res1.2 cells resistant to caspase-8 and caspase-9 fragments and that cisplatin-induced, initiator-caspase independent caspase-3/7 activation was necessary to overcome this resistance. Finally, the results demonstrated that detection of cleaved caspase fragments alone might be insufficient as a marker of caspase activity and ensuing apoptosis induction

Periconceptional Maternal Folic Acid Use of 400 µg per Day Is Related to Increased Methylation of the IGF2 Gene in the Very Young Child

Background: Countries worldwide recommend women planning pregnancy to use daily 400 mg of synthetic folic acid in the periconceptional period to prevent birth defects in children. The underlying mechanisms of this preventive effect are not clear, however, epigenetic modulation of growth processes by folic acid is hypothesized. Here, we investigated whether periconceptional maternal folic acid use and markers of global DNA methylation potential (S-adenosylmethionine and S-adenosylhomocysteine blood levels) in mothers and children affect methylation of the insulin-like growth factor 2 gene differentially methylation region (IGF2 DMR) in the child. Moreover, we tested whether the methylation of the IGF2 DMR was independently associated with birth weight. Methodology/Principal Findings: IGF2 DMR methylation in 120 children aged 17 months (SD 0.3) of whom 86 mothers had used and 34 had not used folic acid periconceptionally were studied. Methylation was measured of 5 CpG dinucleotides covering the DMR using a mass spectrometry-based method. Children of mother who used folic acid had a 4.5% higher methylation of the IGF2 DMR than children who were not exposed to folic acid (49.5% vs. 47.4%; p = 0.014). IGF2 DMR methylation of the children also was associated with the S-adenosylmethionine blood level of the mother but not of the child (+1.7% methylation per SD S-adenosylmethionine; p = 0.037). Finally, we observed an inverse independent association between IGF2 DMR methylation and birth weight (-1.7% methylation per SD birthweight; p = 0.034). Conclusions: Periconceptional folic acid use is associated with epigenetic changes in IGF2 in the child that may affect intrauterine programming of growth and development with consequences for health and disease throughout life. These results indicate plasticity of IGF2 methylation by periconceptional folic acid use